54 results on '"Rheinberger HJ"'
Search Results
2. Claude Bernard and life in the laboratory.
- Author
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Rheinberger HJ
- Subjects
- France, History, 19th Century, Knowledge, Laboratories, Biomedical Research history, Physiology history
- Abstract
Much has been written on Claude Bernard as a relentless promoter of the experimental method in physiology. Although the paper will touch Bernard's experimental intuitions and his experimental practice as well, its focus is slightly different. It will address the laboratory, that is, the space in which experimentation in the life sciences takes place, and it will analyze the scattered remarks that Bernard made on the topic both in his books and in his posthumously published writings. The paper is divided into four parts. The introduction briefly sketches the coming into being of the physiological laboratory in the first half of the nineteenth century. The second section will give an overview of Claude Bernard's own itinerary in physiology and his personal laboratory experience. The third part of the paper will have a look at the image of the laboratory that Claude depicted in his Introduction to Experimental Medicine. In the subsequent section and by contrast, the image of the laboratory will come into focus as it can be reconstructed from Bernard's notebook that he kept between 1850 and 1860, the Cahier rouge. Finally, the fifth part of the paper will spotlight Claude Bernard's comparison of the sciences and the arts and their respective practices. A brief concluding statement tries to summarize Bernard's epistemological position toward experimentally practiced science., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
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3. Postscriptum.
- Author
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Rheinberger HJ
- Published
- 2022
- Full Text
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4. „Ordnung und Organisation“. Interview zur Historiographie der Biologie mit Hans-Jörg Rheinberger und Peter McLaughlin*.
- Author
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Grote M, Te Heesen A, McLaughlin P, and Rheinberger HJ
- Published
- 2021
- Full Text
- View/download PDF
5. Cycles and circulation: a theme in the history of biology and medicine.
- Author
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Hopwood N, Müller-Wille S, Browne J, Groeben C, Kuriyama S, van der Lugt M, Giglioni G, Nyhart LK, Rheinberger HJ, Dröscher A, Anderson W, Anker P, Grote M, and van de Wiel L
- Subjects
- History, 15th Century, History, 16th Century, History, 17th Century, History, 18th Century, History, 19th Century, History, 20th Century, History, 21st Century, History, Ancient, History, Medieval, Biology history, History of Medicine, Philosophy history
- Abstract
We invite systematic consideration of the metaphors of cycles and circulation as a long-term theme in the history of the life and environmental sciences and medicine. Ubiquitous in ancient religious and philosophical traditions, especially in representing the seasons and the motions of celestial bodies, circles once symbolized perfection. Over the centuries cyclic images in western medicine, natural philosophy, natural history and eventually biology gained independence from cosmology and theology and came to depend less on strictly circular forms. As potent 'canonical icons', cycles also interacted with representations of linear and irreversible change, including arrows, arcs, scales, series and trees, as in theories of the Earth and of evolution. In modern times life cycles and reproductive cycles have often been held to characterize life, in some cases especially female life, while human efforts selectively to foster and disrupt these cycles have harnessed their productivity in medicine and agriculture. But strong cyclic metaphors have continued to link physiology and climatology, medicine and economics, and biology and manufacturing, notably through the relations between land, food and population. From the grand nineteenth-century transformations of matter to systems ecology, the circulation of molecules through organic and inorganic compartments has posed the problem of maintaining identity in the face of flux and highlights the seductive ability of cyclic schemes to imply closure where no original state was in fact restored. More concerted attention to cycles and circulation will enrich analyses of the power of metaphors to naturalize understandings of life and their shaping by practical interests and political imaginations., (© 2021. The Author(s).)
- Published
- 2021
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6. Wissenschaftsgeschichte heute.
- Author
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Rheinberger HJ
- Published
- 2018
- Full Text
- View/download PDF
7. Afterword: Instruments as media, media as instruments.
- Author
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Rheinberger HJ
- Subjects
- Communication, Research Design, Science methods
- Abstract
The collection of essays comes under the heading of two catchwords: instruments and media. This Afterword looks at their interaction and roles in exploring the characteristics of living beings throughout history, especially their melding and gliding into each other. Before turning to the papers, I will make some more general remarks on instruments and media in scientific, and in particular, biological research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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8. Preparations, models, and simulations.
- Author
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Rheinberger HJ
- Subjects
- History, 17th Century, History, 18th Century, History, 19th Century, History, 20th Century, History, 21st Century, Biological Science Disciplines history, Computer Simulation history, Models, Biological, Specimen Handling history
- Abstract
This paper proposes an outline for a typology of the different forms that scientific objects can take in the life sciences. The first section discusses preparations (or specimens)--a form of scientific object that accompanied the development of modern biology in different guises from the seventeenth century to the present: as anatomical-morphological specimens, as microscopic cuts, and as biochemical preparations. In the second section, the characteristics of models in biology are discussed. They became prominent from the end of the nineteenth century onwards. Some remarks on the role of simulations--characterising the life sciences of the turn from the twentieth to the twenty-first century--conclude the paper.
- Published
- 2015
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9. Shaping biomedical objects across history and philosophy:a conversation with Hans-Jörg Rheinberger.
- Author
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García-Sancho M, González-Silva M, Jesús Santesmases M, and Rheinberger HJ
- Subjects
- History, 20th Century, History, 21st Century, Biology history, Biomedical Research history, Knowledge, Philosophy history
- Abstract
Historical epistemology, according to the historian of science Hans-Jörg Rheinberger, is a space through which "to take experimental laboratory work into the realm of philosophy". This key concept, together with the crucial events and challenges of his career, were discussed in a public conversation which took place on the occasion of Rheinberger's retirement. By making sense of natural phenomena in the laboratory, the act of experimenting shapes the object; it is this shaping which became the core of Rheinberger's own research across biology and philosophy into history. For his intellectual agenda, a history of the life sciences so constructed became "epistemologically demanding".
- Published
- 2014
10. [Gaston Bachelard and Albert Flocon the meeting of a philosopher and an engraver].
- Author
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Rheinberger HJ
- Abstract
The paper focuses on the collaboration between the philosopher of science Gaston Bachelard and the copper engraver Albert Flocon during the first decade after World War II. The exchange resulted in a number of books whose content is discussed.
- Published
- 2013
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11. [Not Available].
- Author
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Epple M, Hård M, Nikolow S, Rheinberger HJ, and Roelcke V
- Published
- 2010
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12. Introduction to "Writing Genomics".
- Author
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Rheinberger HJ
- Subjects
- Computational Biology, Historiography, Humans, Philosophy, Biological Science Disciplines, Genomics, Metaphysics
- Published
- 2010
13. Introduction. History of molecular biology.
- Author
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de Chadarevian S and Rheinberger HJ
- Subjects
- Biotechnology history, History, 20th Century, History, 21st Century, Historiography, Molecular Biology history
- Published
- 2009
- Full Text
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14. Recent science and its exploration: the case of molecular biology.
- Author
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Rheinberger HJ
- Subjects
- History, 20th Century, Biomedical Research history, Biotechnology history, Historiography, Molecular Biology history
- Abstract
This paper is about the interaction and the intertwinement between history of science as a historical process and history of science as the historiography of this process, taking molecular biology as an example. In the first part, two historical shifts are briefly characterized that appear to have punctuated the emergence of molecular biology between the 1930s and the 1980s, one connected to a new generation of analytical apparatus, the other to properly molecular tools. The second part concentrates on the historiography of this development. Basically, it distinguishes three phases. The first phase was largely dominated by accounts of the actors themselves. The second coincided with the general 'practical turn' in history of science at large, and today's historical appropriations of the molecularization of the life sciences appear to be marked by the changing disciplinary status of the science under review. In a closing remark, an argument is made for differentiating between long-range, middle-range and short-range perspectives in dealing with the history of the sciences.
- Published
- 2009
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15. Journals under threat: a joint response from history of science, technology and medicine editors.
- Author
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Cook H, Hardy A, Andersen H, Ariew R, Feingold M, Bag AK, Barrow-Green J, van Dalen B, Benson K, Beretta M, Blay M, Bleker J, Stolberg M, Borck C, Bowker G, Star SL, Bucciantini M, Camerota M, Buchwald J, Gray J, Cappelletti V, Cimino G, Carson C, Clark M, Keller A, Cline R, Clucas S, Gaukroger S, Corry L, Métraux A, Renn J, Dolan B, Luckin B, Duerbeck H, Orchiston W, Epple M, Hård M, Rheinberger HJ, Roelcke V, Farber P, Fissell M, Packard R, Fox R, Frasca-Spada M, French S, Good J, Hackmann W, Halleux R, Holmqvist B, Home R, Hoskin M, Inkster I, Jardine N, Levere T, Lightman B, Lüthy C, Lynch M, McCluskey S, Ruggles C, Morris P, Morus IR, Nelson EC, Nicholson I, Olesko K, Pérez L, Rigden J, Stuewer RH, Samsó J, Schaffer S, Schappacher N, Staudenmaier J, Strom C, Unschuld P, Weingart P, Zamecki S, and Zuidervaart H
- Subjects
- Germany, Humans, Editorial Policies, History of Medicine, Journal Impact Factor, Periodicals as Topic, Science, Technology
- Published
- 2009
16. Journals under threat. A joint response from History of Science, Technology and Medicine editors.
- Author
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Fox R, Andersen H, Ariew R, Feingold M, Bag AK, Barrow-Green J, van Dalen B, Benson K, Beretta M, Blay M, Borck C, Bowker G, Star SL, Bucciantini M, Camerota M, Buchwald J, Gray J, Cappelletti V, Cimino G, Clark M, Keller A, Cline R, Clucas S, Gaukroger S, Cook H, Hardy A, Corry L, Métraux A, Renn J, Dolan B, Luckin B, Duerbeck H, Orchiston W, Epple M, Hård M, Rheinberger HJ, Roelcke V, French S, Farber P, Fissell M, Packard R, Good J, Hackmann W, Halleux R, Holmqvist B, Hoskin M, Inkster I, Spada MF, Jardine N, Levere T, Lightman B, Lüthy C, Lynch M, McCluskey S, Ruggles C, Morris P, Nelson EC, Nicholson I, Olesko K, Peréz L, Morus IR, Rigden J, Stuewer RH, Samsó J, Schaffer S, Schappacher N, Strom C, Unschuld P, Weingart P, Zamecki S, and Zuidervaart H
- Subjects
- Europe, Humans, Netherlands, Periodicals as Topic standards, Periodicals as Topic trends
- Published
- 2009
17. Race and genomics. Old wine in new bottles? Documents from a transdisciplinary discussion.
- Author
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Müller-Wille S and Rheinberger HJ
- Subjects
- Genome, Human, History, 19th Century, History, 20th Century, History, 21st Century, Humans, Anthropology, Physical history, Genomics history, Racial Groups history
- Published
- 2008
- Full Text
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18. [Cultures of experiment].
- Author
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Rheinberger HJ
- Subjects
- Cell Culture Techniques methods, Cell Culture Techniques trends, History, 20th Century, Knowledge, Cell Culture Techniques history, Directed Molecular Evolution history, Molecular Biology history
- Abstract
It is generally accepted that the development of modern science is rooted in experiment. Yet for a long time, experimentation did not occupy a prominent role in history of science. With the practical turn in science studies, this has begun to change. This paper is concerned with cultures of experiment. In the first part, a suggestion is made as to how the concept of experimental culture can be used to go beyond a history of disciplines. In the second part, a particular experimental culture in the life sciences is looked at more closely. A survey is given on the changing forms of in vitro experimentation, that is, on analyzing biological functions in a test tube.
- Published
- 2007
- Full Text
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19. [Research on recent science: the example of molecular biology].
- Author
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Rheinberger HJ
- Subjects
- Europe, History, 20th Century, History, 21st Century, North America, Biological Science Disciplines history, Biotechnology history, Molecular Biology history, Research history
- Abstract
The essay thematizes historiographical problems of research on recent history of science on the example of the history of molecular biology. First, a short survey of the history of molecular biology and its possible periodization is given. Second, the parallel development of the work of historians on the emergence of molecular biology is analyzed. Finally, a suggestion for further historical research is made that takes into account three different time perspectives: short range, middle range, and long-term.
- Published
- 2006
20. Alfred Kühn (1885-1968) and developmental evolution.
- Author
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Laubichler MD and Rheinberger HJ
- Subjects
- Biological Evolution, History, 20th Century, Kynurenine genetics, Kynurenine physiology, Developmental Biology history, Genetics history, Physiology history
- Abstract
Alfred Kühn (1885-1968) was known as one of the most comprehensive zoologists of his time. His research program in developmental physiological genetics was one of the first successful attempts to integrate the experimental study of development and heredity. It led him to discover the first known reaction chain from gene to phenotype. Kühn also foresaw many elements of modern evolutionary developmental biology and as a student of Weismann and mentor to many developmental geneticists of the late 20th century directly connects Weismann with molecular developmental genetics., (Copyright 2004 Wiley-Liss, Inc.)
- Published
- 2004
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21. History of science and the practices of experiment.
- Author
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Rheinberger HJ
- Subjects
- Europe, History, 20th Century, Biological Science Disciplines history, Historiography, Philosophy history, Research history
- Published
- 2001
22. Mendelian inheritance in Germany between 1900 and 1910. The case of Carl Correns (1864-1933).
- Author
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Rheinberger HJ
- Subjects
- Fertilization, Germany, History, 19th Century, History, 20th Century, Pisum sativum genetics, Pisum sativum physiology, Zea mays genetics, Zea mays physiology, Genetics history, Plants genetics
- Abstract
Carl Correns (1864-1933) came to recognize Mendel's rules between 1894 and 1900 while trying to find out the mechanism of xenia, that is, the direct influence of the fertilizing pollen on the mother plant in maize and peas among other species. In this paper, I am concerned with the ten years of Correns' work after the annus mirabilis of 1900 until 1910, when the main outlines of the new science of genetics had been established. It is generally assumed that after 1900 Correns quickly began probing the limits of Mendelian inheritance, both as far as the explanatory force of formal transmission genetics and the generality of Mendel's laws are concerned. A careful examination of his papers however shows that he was much more interested in the scope of Mendelian inheritance than in its limits. Even his work with variegated Mirabilis plants, which historiographical folklore still presents as a result of Correns' growing interest in cytoplasmic inheritance, can be shown to have been conducted to corroborate just the opposite, namely, the validity of the nuclear paradigm. The paper will show that Correns' research results in those years (among them the Mendelian inheritance of sex in higher plants) were the outcome of a complex experimental program which involved breeding experiments with dozens of different species.
- Published
- 2000
- Full Text
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23. [Carl Correns' experiments with Pisum, 1896-1899].
- Author
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Rheinberger HJ
- Subjects
- History, 19th Century, Hybridization, Genetic, Pisum sativum genetics, Research Design
- Abstract
The circumstances under which classical genetics became established at the turn of the nineteenth century have become an integral part of the standard narrative on the history of genetics. Yet, despite considerable scholarly efforts, it has remained a matter of debate how exactly the so-called 'rediscovery' of Mendel's laws came about around 1900. In this situation, unpublished research records can be invaluable tools to arrive at a more substantial and more satisfying picture of the order of historical events. This paper makes extended use of the research protocols covering Carl Correns' hybridisation experiments with Pisum sativum between 1896 and 1899. The resulting reconstruction sketches the portrait of a scientist following a particular research question--xenia--struggling with his experimental material, and slowly building up an epistemic regime in which questions and observations could acquire a relevance which did not strike Correns when he first took note of them. The microhistorical gaze through the magnifying glass of research notes reveals the kind of delays that appear to be constitutive for empirically-driven thinking in general. The research notes of Correns help not only to make this point, they also display some of the intricacies and material peculiarities which characterise the experimental process of hybridisation and the particular type of inferences it allows one to make.
- Published
- 2000
24. Ephestia: the experimental design of Alfred Kühn's physiological developmental genetics.
- Author
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Rheinberger HJ
- Subjects
- Animals, Germany, History, 20th Century, Genetics history, Moths growth & development, Moths physiology, Physiology history, Research Design
- Abstract
Much of the early history of developmental and physiological genetics in Germany remains to be written. Together with Carl Correns and Richard Goldschmidt, Alfred Kühn occupies a special place in this history. Trained as a zoologist in Freiburg im Breisgau, he set out to integrate physiology, development and genetics in a particular experimental system based on the flour moth Ephestia kühniella Zeller. This paper is meant to reconstruct the crucial steps in the experimental pathway that led Kühn and his collaborators at the University of Göttingen, and later at the Kaiser Wilhelm Institutes of Biology and Biochemistry in Berlin, to formulate, in their specific way, what later became known as the "one gene - one enzyme hypothesis." Special attention will be given to the interaction of the different parts of Kühn's Ephestia-based project, which were rooted in different research traditions. The paper retraces how, roughly between 1925 and 1945, these elements came to form a mixed experimental set-up composed of genetic, embryological, physiological and, finally, biochemical constituents. Accordingly, emphasis is laid on the development of the terminology in which the results were cast, and how it reflected the hybrid state of an experimental system successively acquiring new epistemic layers.
- Published
- 2000
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25. Ernest F. Gale and protein synthesis: the difficulties of analysing a complex system.
- Author
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Rheinberger HJ
- Subjects
- Amino Acids metabolism, Anti-Bacterial Agents pharmacology, Bacterial Proteins biosynthesis, Cell-Free System, England, History, 20th Century, Staphylococcus aureus drug effects, Staphylococcus aureus metabolism, beta-Galactosidase history, Bacterial Proteins history
- Published
- 1998
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26. Modulation of IgE reactivity of allergens by site-directed mutagenesis: potential use of hypoallergenic variants for immunotherapy.
- Author
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Ferreira F, Ebner C, Kramer B, Casari G, Briza P, Kungl AJ, Grimm R, Jahn-Schmid B, Breiteneder H, Kraft D, Breitenbach M, Rheinberger HJ, and Scheiner O
- Subjects
- Allergens biosynthesis, Allergens chemistry, Anaphylaxis prevention & control, Antigens, Plant, Binding Sites, Antibody, DNA Primers, Genetic Variation, Humans, Mutagenesis, Site-Directed, Plant Proteins biosynthesis, Plant Proteins chemistry, Poaceae, Point Mutation, Recombinant Proteins chemistry, Recombinant Proteins immunology, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Allergens immunology, Hypersensitivity, Immediate therapy, Immunoglobulin E immunology, Immunotherapy methods, Plant Proteins immunology
- Abstract
Specific immunotherapy is an efficient treatment for patients suffering from type I allergy. The mechanisms underlying successful immunotherapy are assumed to operate at the level of T helper cells, leading to a modulation of the immune response to allergens. During immunotherapy, increasing doses of allergens are given on a regular basis, and the beneficial effects for the patient depend on the concentration of allergen used. On the other hand, the risk of IgE-mediated anaphylactic side effects also increase with the amount of allergen applied per injection. Therefore, we have proposed the use of hypoallergenic (low IgE binding activity) forms of allergens for immunotherapy. We evaluated by site-directed mutagenesis the contributions of individual amino acid residues/positions for IgE binding to Bet v 1, the major allergen of birch pollen. We found that IgE binding to Bet v 1 depended on at least six amino acid residues/positions. Immunoblot analyses and inhibition experiments showed that the multiple-point Bet v 1 mutant exhibited extremely low reactivity with serum IgE from birch pollen-allergic patients. In vivo (skin prick) tests showed that the potency of the multiple-point mutant to induce typical urticarial type I reactions in pollen-allergic patients was significantly lower than for wild-type Bet v 1. Proliferation assays of allergen-specific T cell clones demonstrated that these six amino acid exchanges in the Bet v 1 sequence did not influence T cell recognition. Thus, the Bet v 1 six-point mutant displayed significantly reduced IgE binding activity, but conserved T cell activating capacity, which is necessary for immunomodulation. The approach described here may be generally applied to produce allergen variants to be used in a safe therapy form of immediate-type allergies.
- Published
- 1998
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27. From the "originary phenomenon" to the "system of pelagic fishery": Johannes Müller (1801-1858) and the relation between physiology and philosophy.
- Author
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Rheinberger HJ
- Subjects
- Germany, History, 19th Century, Humans, Natural History history, Philosophy history, Physiology history
- Published
- 1998
28. Immunological and biological properties of Bet v 4, a novel birch pollen allergen with two EF-hand calcium-binding domains.
- Author
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Engel E, Richter K, Obermeyer G, Briza P, Kungl AJ, Simon B, Auer M, Ebner C, Rheinberger HJ, Breitenbach M, and Ferreira F
- Subjects
- Allergens chemistry, Allergens genetics, Amino Acid Sequence, Antigens, Plant, Binding Sites, Calcium-Binding Proteins chemistry, Calcium-Binding Proteins genetics, Cloning, Molecular, DNA, Complementary chemistry, DNA, Complementary isolation & purification, Immunoglobulin E metabolism, Iontophoresis, Molecular Sequence Data, Plant Proteins chemistry, Plant Proteins genetics, Pollen chemistry, Pollen genetics, Recombinant Proteins immunology, Recombinant Proteins metabolism, Sequence Alignment, Allergens immunology, Calcium metabolism, Calcium-Binding Proteins immunology, Plant Proteins immunology, Pollen immunology
- Abstract
We have isolated a cDNA clone coding for a birch pollen allergen, Bet v 4. The deduced amino acid sequence of Bet v 4 contained two typical EF-hand calcium-binding domains. Sequence similarities of Bet v 4 to calmodulin are primarily confined to the calcium-binding domains. However, significant sequence similarities extending outside the Ca2+-binding sites were found with a recently described group of pollen-specific allergens of Brassica and Bermuda grass. Both EF-hand domains of Bet v 4 are able to bind Ca2+, as demonstrated by 45Ca2+ blot overlay of wild type and calcium-binding deficient mutants of Bet v 4. Among pollen-allergic patients, protein-bound Ca2+ was not an absolute requirement for IgE recognition of Bet v 4. However, disruption of the carboxyl-terminal Ca2+-binding domain indicated that most IgE antibodies from allergic patients are directed against this site. IgE inhibition experiments suggested that Bet v 4 represents a highly cross-reactive pollen allergen. Pre-absorption of allergic sera with Bet v 4 drastically reduced IgE binding to proteins of similar molecular weight in pollen extracts from distantly related plant species (e.g. timothy grass, mugwort, lily) but not in extracts from plant-derived foodstuff. To test for a possible biological role in pollen germination and tube growth, we introduced recombinant Bet v 4 protein into growing lily pollen tubes by iontophoresis. As a result, cytoplasmic streaming stopped in the vicinity of the electrode tip, and a slight depolarization of the membrane voltage was measured. These effects were not observed with Ca2+-binding deficient mutants of Bet v 4. Thus, Bet v 4 and homologous proteins represent a new class of pollen-specific Ca2+-binding allergens that may have a physiological role as inhibitors of cytoplasmic streaming in outgrowing pollen tubes.
- Published
- 1997
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29. Cytoplasmic particles in Brussels (Jean Brachet, Hubert Chantrenne, Raymond Jeener) and at Rockefeller (Albert Claude), 1935-1955.
- Author
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Rheinberger HJ
- Subjects
- Animals, Belgium, History, 20th Century, Humans, New York City, Research history, Molecular Biology history
- Published
- 1997
30. Comparing experimental systems: protein synthesis in microbes and in animal tissue at Cambridge (Ernest F. Gale) and at the Massachusetts General Hospital (Paul C. Zamecnik), 1945-1960.
- Author
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Rheinberger HJ
- Subjects
- Animals, History, 20th Century, Humans, United Kingdom, United States, Universities history, Biochemistry history, Histology history, Laboratories history, Laboratories, Hospital history, Microbiology history, Proteins history
- Published
- 1996
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31. Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v 1: potential use of hypoallergenic isoforms for immunotherapy.
- Author
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Ferreira F, Hirtenlehner K, Jilek A, Godnik-Cvar J, Breiteneder H, Grimm R, Hoffmann-Sommergruber K, Scheiner O, Kraft D, Breitenbach M, Rheinberger HJ, and Ebner C
- Subjects
- Allergens chemistry, Allergens therapeutic use, Amino Acid Sequence, Antigens, Plant, Base Sequence, Clone Cells, Cloning, Molecular, Electrophoresis, Polyacrylamide Gel, Epitopes, Humans, Immunoblotting, Immunotherapy methods, Molecular Sequence Data, Plant Proteins chemistry, Plant Proteins genetics, Plant Proteins therapeutic use, Pollen chemistry, Recombinant Proteins immunology, Recombinant Proteins isolation & purification, Recombinant Proteins therapeutic use, Sequence Analysis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Allergens immunology, Hypersensitivity therapy, Plant Proteins immunology, Pollen immunology, T-Lymphocytes immunology
- Abstract
We dissected the T cell activation potency and the immunoglobulin (Ig) E-binding properties (allergenicity) of nine isoforms of Bet v 1 (Bet v 1a-Bet v 1l), the major birch pollen allergen. Immunoblot experiments showed that Bet v 1 isoforms differ in their ability to bind IgE from birch pollen-allergic patients. All patients tested displayed similar IgE-binding patterns toward each particular isoform. Based on these experiments, we grouped Bet v 1 isoforms in three classes: molecules with high IgE-binding activity (isoforms a, e, and j), intermediate IgE-binding (isoforms b, c, and f), and low/no IgE-binding activity (isoforms d, g, and 1). Bet v 1a, a recombinant isoform selected from a cDNA expression library using IgE immunoscreening exhibited the highest IgE-binding activity. Isoforms a, b, d, e, and 1 were chosen as representatives from the three classes for experimentation. The potency of each isoallergen to activate T lymphocytes from birch pollen-allergic patients was assayed using peripheral blood mononuclear cells, allergen-specific T cell lines, and peptide-mapped allergen-specific T cell clones. Among the patients, some displayed a broad range of T cell-recognition patterns for Bet v 1 isoforms whereas others seemed to be restricted to particular isoforms. In spite of this variability, the highest scores for T cell proliferative responses were observed with isoform d (low IgE binder), followed by b, 1, e, and a. In vivo (skin prick) tests showed that the potency of isoforms d and 1 to induce typical urticarial type 1 reactions in Bet v 1-allergic individuals was significantly lower than for isoforms a, b, and e. Taken together, our results indicate that hypoallergenic Bet v 1 isoforms are potent activators of allergen-specific T lymphocytes, and Bet v 1 isoforms with high in vitro IgE-binding activity and in vivo allergenicity can display low T cell antigenicity. Based on these findings, we propose a novel approach for immunotherapy of type I allergies: a treatment with high doses of hypoallergenic isoforms or recombinant variants of atopic allergens. We proceed on the assumption that this measure would modulate the quality of the T helper cell response to allergens in vivo. The therapy form would additionally implicate a reduced risk of anaphylactic side effects.
- Published
- 1996
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32. Beyond nature and culture: a note on medicine in the age of molecular biology.
- Author
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Rheinberger HJ
- Subjects
- Genetic Therapy history, History, 20th Century, Humans, Molecular Biology history
- Abstract
This paper is divided into two parts. In the first, I examine the relations among molecular biology, gene technology, and medicine, as well as some aspects of the consequences of these relations with respect to the human genome project. I argue that the prevailing momentum of early molecular biology resided in creating the technical means for an extracellular representation of intracellular configurations. As such, its medical impact was rather limited. With the advent of recombinant DNA technologies, a radical change of perspective ensued. The momentum of gene technology is based on the prospects of an intracellular representation of extracellular projects--the "rewriting" of life. Its medical impact is potentially unlimited. In the second part, I question the very opposition between nature and culture that implicitly underlies the notion of medicine as a "cultural system." I argue that both on a macroscopic level (global ecological changes) and on a microscopic level (genetic engineering), the "natural" and the "social" are no longer to be seen as ontologically different. In its uncanny oscillation between retrospection and foresight, between description and proclamation, and between assertion and hesitatiion, this essay translates an uneasiness that I have not been able to overcome while writing it. The essay conveys the tangled views of a hybrid author who himself cannot but oscillate between the perspectives of an actor in the field of molecular biology, a participant in the field of science studies, and a citizen.
- Published
- 1995
- Full Text
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33. From microsomes to ribosomes: "strategies" of "representation".
- Author
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Rheinberger HJ
- Subjects
- History, 19th Century, History, 20th Century, Humans, Microbiology history, Research history
- Published
- 1995
- Full Text
- View/download PDF
34. Experiment and orientation: early systems of in vitro protein synthesis.
- Author
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Rheinberger HJ
- Subjects
- History, Modern 1601-, United States, Molecular Biology history, Research history
- Published
- 1993
- Full Text
- View/download PDF
35. Experiment, difference, and writing: I. Tracing protein synthesis.
- Author
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Rheinberger HJ
- Subjects
- History, Modern 1601-, Biochemistry history, Chemistry history, Molecular Biology history, Research history
- Published
- 1992
- Full Text
- View/download PDF
36. Experiment, difference, and writing: II. The laboratory production of transfer RNA.
- Author
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Rheinberger HJ
- Subjects
- History, Modern 1601-, United States, Academies and Institutes history, Genetics history, Laboratories history, Research history
- Published
- 1992
- Full Text
- View/download PDF
37. The function of the translating ribosome: allosteric three-site model of elongation.
- Author
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Rheinberger HJ
- Subjects
- Allosteric Site, Anti-Bacterial Agents pharmacology, Base Sequence, Molecular Sequence Data, Peptide Chain Elongation, Translational, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Transfer metabolism, Ribosomes drug effects, Models, Biological, Protein Biosynthesis, Ribosomes metabolism
- Abstract
During the last decade, a new model for the ribosomal elongation cycle has emerged. It is based on the finding that eubacterial ribosomes possess 3 tRNA binding sites. More recently, this has been confirmed for archaebacterial and eukaryotic ribosomes as well, and thus appears to be a universal feature of the protein synthetic machinery. Ribosomes from organisms of all 3 kingdoms harbor, in addition to the classical P and A sites, an E site (E for exit), into which deacylated tRNA is displaced during translocation, and from which it is expelled by the binding of an aminoacyl-tRNA to the A site at the beginning of the subsequent elongation round. The main features of the allosteric 3-site model of ribosomal elongation are the following: first, the third tRNA binding site is located 'upstream' adjacent to the P site with respect to the messenger, ie on the 5'-side of the P site. Second, during translocation, deacylated tRNA does not leave the ribosome from the P site, but co-translocates from the P site to the E site--when peptidyl-tRNA translocates from the A site to the P site. Third, deacylated tRNA is tightly bound to the E site in the post-translocational state, where it undergoes codon--anticodon interaction. Fourth, the elongating ribosome oscillates between 2 main conformations: (i), the pre-translocational conformer, where aminoacyl-tRNA (or peptidyl-tRNA) and peptidyl-tRNA (or deacylated tRNA) are firmly bound to the A and P sites, respectively; and (ii), the post-translocational conformer, where peptidyl-tRNA and deacylated tRNA are firmly bound to the P and E sites, respectively. The transition between the 2 states is regulated in an allosteric manner via negative cooperatively. It is modulated in a symmetrical fashion by the 2 elongation factors Tu and G. An elongating ribosome always maintains 2 high-affinity tRNA binding sites with 2 adjacent codon--anticodon interactions. The allosteric transition from the post- to the pre-translocational state is involved in the accuracy of aminoacyl-tRNA selection, and the maintenance of 2 codon--anticodon interactions helps to keep the messenger in frame during translation.
- Published
- 1991
- Full Text
- View/download PDF
38. Partial release of AcPhe-Phe-tRNA from ribosomes during poly(U)-dependent poly(Phe) synthesis and the effects of chloramphenicol.
- Author
-
Rheinberger HJ and Nierhaus KH
- Subjects
- Binding Sites, Kinetics, Protein Biosynthesis drug effects, Puromycin metabolism, RNA, Transfer, Phe metabolism, Ribosomes drug effects, Chloramphenicol pharmacology, Escherichia coli metabolism, Peptide Biosynthesis, Peptides, Poly U metabolism, RNA, Transfer, Amino Acyl metabolism, Ribosomes metabolism
- Abstract
Poly(U)-programmed 70S ribosomes can be shown to be 80% to 100% active in binding the peptidyl-tRNA analogue AcPhe-tRNA to their A or P sites, respectively. Despite this fact, only a fraction of such ribosomes primed with AcPhe-tRNA participate in poly(U)-directed poly(Phe) synthesis (up to 65%) at 14 mM Mg2+ and 160 mM NH4+. Here it is demonstrated that the apparently 'inactive' ribosomes (greater than or equal to 35%) are able to participate in peptide-bond formation, but lose their nascent peptidyl-tRNA at the stage of Ac(Phe)n-tRNA, with n greater than or equal to 2. The relative loss of early peptidyl-tRNAs is largely independent of the degree of initial saturation with AcPhe-tRNA and is observed in a poly(A) system as well. This observation resolves a current controversy concerning the active fraction of ribosomes. The loss of Ac(Phe)n-tRNA is reduced but still significant if more physiological conditions for Ac(Phe)n synthesis are applied (3 mM Mg2+, 150 mM NH4+, 2 mM spermidine, 0.05 mM spermine). Chloramphenicol (0.1 mM) blocks the puromycin reaction with AcPhe-tRNA as expected but, surprisingly, does not affect the puromycin reaction with Ac(Phe)2-tRNA nor peptide bond formation between AcPhe-tRNA and Phe-tRNA. The drug facilitates the release of Ac(Phe)2-4-tRNA from ribosomes at 14 mM Mg2+ while it hardly affects the overall synthesis of poly(Phe) or poly(Lys).
- Published
- 1990
- Full Text
- View/download PDF
39. [Buffon: time, change and history].
- Author
-
Rheinberger HJ
- Subjects
- Animals, France, History, 18th Century, Humans, Life Style, Social Change, Time, Biological Evolution, Philosophy history
- Abstract
There is a longstanding and ongoing controversy about whether Buffon is to be regarded as a forerunner of evolutionism in the eighteenth century, or even as one of the founders of transformistic biology. There are good reasons to deny this claim. There are good reasons even to deny that the question which is going to be answered negatively is of particular importance. The present paper addresses the issue from a different angle. It analyzes the concept of time operative in the natural history writings of Buffon, and it delineates the articulation of the concepts of time, change, and history with its organizing impact on Buffon's discourse on earth and organisms. It is argued that although with his species concept Buffon tries to introduce the classical notion of a physical system into biology, in order to do so, he has to subvert it by an element of time. This guides him in considering various aspects of organic change, but by itself does not lead to a general perspective of transformation. On the other hand, in his Epoques de la nature, Buffon introduces a general law of geological change, thus arriving at something which could be called a physically intelligible history. The conquest of natural history by physics, in one and the same movement, leads to a subversion of physical geology by history, and prevents biology from becoming evolutionistic in the sense in which the nineteenth century understands this term.
- Published
- 1990
40. Crystallization of Escherichia coli ribosomes.
- Author
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Wittmann HG, Müssig J, Piefke J, Gewitz HS, Rheinberger HJ, and Yonath A
- Subjects
- Cell Fractionation, Centrifugation, Density Gradient, Crystallization, Microscopy, Electron, Poly U metabolism, Escherichia coli ultrastructure, Ribosomes ultrastructure
- Published
- 1982
- Full Text
- View/download PDF
41. [Not Available].
- Author
-
Rheinberger HJ
- Subjects
- France, Germany, History, Modern 1601-, Physiology history
- Published
- 1987
42. Allosteric interactions between the ribosomal transfer RNA-binding sites A and E.
- Author
-
Rheinberger HJ and Nierhaus KH
- Subjects
- Acylation, Allosteric Site, Guanosine Triphosphate metabolism, Guanylyl Imidodiphosphate metabolism, Peptide Chain Elongation, Translational, Peptide Elongation Factor Tu metabolism, Peptide Elongation Factor Tu pharmacology, RNA, Transfer, Amino Acyl metabolism, Escherichia coli metabolism, RNA, Bacterial metabolism, RNA, Transfer metabolism, Ribosomes metabolism
- Abstract
We have previously proposed a three-site model for the elongation cycle. The model is characterized by the presence of two tRNAs on the ribosome before and after translocation. We have already shown a first consequence of the model, namely that the translocation reaction is not coupled with a release of deacylated tRNA. Here we demonstrate the following conclusions. Occupation of the A site triggers the tRNA release from the E site, i.e. the A site occupation induces a drastic decrease in the affinity of the E site for deacylated tRNA. In the concentration range of deacylated tRNA in which a ribosome binds a second tRNA in addition to that one already present at the P site the deacylated tRNA does not compete for one and the same binding site with an A site ligand (AcPhe-tRNA) at 37 degrees C. It follows that the second deacylated tRNA binds to a site, the E site, which is physically distinct from the A site. When the ribosome binds a deacylated tRNA at the E site (in addition to a tRNA at the P site), the A site cannot be occupied by AcPhe-tRNA at 0 degree C and only poorly by the ternary complex elongation factor Tu . Phe-tRNA . guanyl-5'-yl imidodiphosphate. At 37 degrees C a significant A site binding is observed, with a corresponding tRNA release from the E site. In contrast, if the E site is free and only the P site occupied, the A site can bind significant amounts of charged tRNA already at 0 degree C. It follows that an occupied E site induces a low-affinity state of the A site. Thus, the ribosome always contains two high-affinity binding sites, which are A and P sites before and P and E sites after translocation. A and E sites are allosterically linked in a bidirectional manner.
- Published
- 1986
43. Preparation procedures of proteins and RNA influence the total reconstitution of 50S subunits from E. coli ribosomes.
- Author
-
Nowotny V, Rheinberger HJ, Nierhaus K, Tesche B, and Amils R
- Subjects
- Bacterial Proteins metabolism, Magnesium, Methods, Nucleic Acid Conformation, Protein Conformation, RNA, Bacterial metabolism, Bacterial Proteins isolation & purification, Escherichia coli metabolism, RNA, Bacterial isolation & purification, Ribosomes metabolism
- Abstract
A two-step procedure has been described for the total reconstitution of 50S ribosomal subunit from E. coli. RNA and proteins are mixed with stoichiometry of 1:1.2 and incubated at 44 degrees C in 4.0 mM Mg2+ followed by a second incubation at 50 degrees C in 20 mM Mg2+ (Dohme and Nierhaus, J. Mol. Biol. 107, 585 (1976)). A modified method recently reported makes use of an altered preparation technique for the RNA and proteins and requires an RNA to protein stoichiometry of 1:2.5 and 7.5 mM Mg2+ in the first incubation (Amils et al., Nucl. Acid Res. 5, 2455 (1978)). The latter requirements are not compatible with the findings obtained with the first procedure. A comparison of the various RNA and protein fractions from the different groups revealed that the Mg2+ dependence of reconstitution is a function of the RNA preparation, whereas the stoichiometry depends upon the technique used for isolation of the protein fraction. The different RNA preparations were compared in the electron microscope.
- Published
- 1980
- Full Text
- View/download PDF
44. Testing an alternative model for the ribosomal peptide elongation cycle.
- Author
-
Rheinberger HJ and Nierhaus KH
- Subjects
- Kinetics, Peptide Elongation Factor G, Peptide Elongation Factors metabolism, Peptides genetics, Poly U genetics, RNA, Transfer, Amino Acyl genetics, Escherichia coli genetics, Peptide Chain Elongation, Translational, Ribosomes metabolism
- Abstract
A kinetic analysis of poly(U)-dependent poly(Phe) synthesis with [14C]tRNAPhe and [3H]phenylalanine demonstrated that, in the course of efficient poly(Phe) synthesis, two tRNAs are present per 70S ribosome at all times, although at least 70% of the poly(Phe)-tRNAPhe is found at the peptidyl-tRNA (P) site. Together with our recent observation of a third tRNA-binding site on Escherichia coli ribosomes, these findings suggest a model for the peptide elongation cycle in which two tRNA molecules are present on the ribosome at both the pre- and the post-translocational state. This model predicts that deacylated tRNA is not released from the P site but translocated to the exit (E) site before release occurs. A series of translocation experiments with deacylated [14C]tRNAPhe at the P site and oligo [( 3H]Phe)-tRNA at the aminoacyl-tRNA (A) site proved that efficient elongation factor G-dependent translocation is not accompanied by a corresponding [14C]tRNAPhe release. However, significant [14C]tRNAPhe release was observed after translocation when an aminoacyl-tRNA was bound to the A site. Thus, deacylated tRNA is not released from the P site but is translocated to the E site, which therefore must be located "upstream" adjacent to the P site. Furthermore, the trigger for the release of deacylated tRNA from the E site is the binding of aminoacyl-tRNA to the A site.
- Published
- 1983
- Full Text
- View/download PDF
45. The ribosomal elongation cycle: tRNA binding, translocation and tRNA release.
- Author
-
Rheinberger HJ, Schilling S, and Nierhaus KH
- Subjects
- Bacterial Proteins isolation & purification, Binding Sites, Chemical Phenomena, Chemistry, Escherichia coli genetics, Escherichia coli metabolism, Protein Binding, Peptide Chain Elongation, Translational, RNA, Ribosomal isolation & purification, RNA, Transfer isolation & purification, Translocation, Genetic
- Published
- 1983
- Full Text
- View/download PDF
46. Naudin, Darwin, Nägeli: Bemerkungen zu den Vererbungsvorstellungen des 19. Jahrhunderts.
- Author
-
Rheinberger HJ
- Subjects
- History, Modern 1601-, Biology history, Genetics history
- Published
- 1983
47. Darwin's experimental natural history.
- Author
-
Rheinberger HJ and McLaughlin P
- Subjects
- History, Modern 1601-, United Kingdom, Biological Evolution, Genetics history
- Published
- 1984
- Full Text
- View/download PDF
48. The ribosomal E site at low Mg2+: coordinate inactivation of ribosomal functions at Mg2+ concentrations below 10 mM and its prevention by polyamines.
- Author
-
Rheinberger HJ and Nierhaus KH
- Subjects
- Allosteric Regulation, Binding Sites, Cell-Free System, Escherichia coli metabolism, Models, Biological, Osmolar Concentration, Peptide Biosynthesis, Phenylalanine metabolism, Poly U genetics, RNA, Transfer, Amino Acyl metabolism, Ribosomes ultrastructure, Magnesium pharmacology, Peptide Chain Elongation, Translational drug effects, Peptides, Polyamines pharmacology, Ribosomes drug effects
- Abstract
Under standard conditions (Mg2+/150 mM NH4+) ribosomes can quantitatively participate in tRNA binding at Mg2+ concentrations of 12 to 15 mM. The overall poly(U)-directed Phe incorporation and the extent of tRNA binding to either P, E or A sites decrease in a parallel manner when the Mg2+ concentration is lowered below 10 mM. At 4 mM the inactivation amounts to about 80%. The coordinate inactivation of all three binding sites is accompanied by an increasing impairment of the ability to translocate A-site bound AcPhe-tRNA to the P site. The translocation efficiency is already reduced at 10 mM Mg2+, and is completely blocked at 6-8 mM. The severe inactivation seen at 6 mM Mg2+ vanishes when the polyamines spermine (0.6 mM) and spermidine (0.4 mM) are present in the assay; tRNA binding again becomes quantitative, the total Phe synthesis even exceeds that observed in the absence of polyamines by a factor of 4. In the presence of polyamines and low Mg2+ (3 and 6 mM) two essential features of the allosteric three-site model (Rheinberger and Nierhaus, J. Biol. Chem. 261, 9133 (1986] are demonstrated. 1) Deacylated tRNA is not released from the P site, but moves to the E site during the course of translocation. 2) Occupation of the E site reduces the A site affinity and vice versa (allosteric interactions between E and A sites). The quality of an in vitro system for protein synthesis can be assessed by two criteria. First, the incubation conditions must allow a near quantitative tRNA binding. Secondly, protein synthesis should proceed with near in vivo rate and accuracy. The 3 mM Mg2+/NH4+/polyamine-system seems to be the best compromise at present between these two requirements.
- Published
- 1987
- Full Text
- View/download PDF
49. Three tRNA binding sites on Escherichia coli ribosomes.
- Author
-
Rheinberger HJ, Sternbach H, and Nierhaus KH
- Subjects
- Binding Sites, Escherichia coli, Peptide Elongation Factors metabolism, RNA, Messenger metabolism, Ribosomes metabolism, RNA, Transfer metabolism, RNA, Transfer, Amino Acyl metabolism, Ribosomes ultrastructure
- Abstract
The binding of N-acetyl-Phe-tRNAPhe (an analogue of peptidyl-tRNA), Phe-tRNAPhe, and deacylated tRNAPhe to poly(U)-programmed tightly coupled 70S ribosomes was studied. The N-acetyl-Phe-tRNAPhe binding is governed by an exclusion principle: not more than one N-acetyl-Phe-tRNAPhe can be bound per ribosome, although this peptidyl-tRNA analogue can be present either at the aminoacyl-tRNA (A) site or the peptidyl-tRNA (P) site. Two Phe-tRNAPhe molecules are accepted by one ribosome in the presence of poly(U). This aminoacyl-tRNA binds enzymatically (in the presence of elongation factor Tu and GTP) and nonenzymatically to the A site and is then transferred to the P site, if that site is free. If this elongation factor G-independent movement is hampered, either by using an incubation temperature of 0 degrees C or by the addition of the translocation inhibitor viomycin, only one Phe-tRNAPhe per ribosome can be bound. The effect of the peptidyltransferase inhibitor chloramphenicol on the binding is similar to that of viomycin. In the absence of poly(U), Phe-tRNAPhe cannot bind to the ribosome. Deacylated [14C]tRNAPhe can bind in three copies to one ribosome. The new third tRNA binding site is called the "E" site. The sequence of filling the sites is P, E, and A. The apparent binding constants for the P and the E sites are both approximately 9 X 10(6) M-1 and that for the A site is 1.3 X 10(6) M-1. In the absence of poly(U), only one deacylated tRNAPhe can be bound per ribosome. This tRNAPhe most likely occupies the P site.
- Published
- 1981
- Full Text
- View/download PDF
50. New aspects of structure, assembly, evolution, and function of ribosomes.
- Author
-
Nierhaus KH, Brimacombe R, Nowotny V, Pon CL, Rheinberger HJ, Wittmann-Liebold B, and Wittmann HG
- Subjects
- Protein Biosynthesis, RNA, Ribosomal, 16S genetics, RNA, Ribosomal, 16S ultrastructure, Ribosomes ultrastructure, Biological Evolution, Ribosomes metabolism
- Published
- 1987
- Full Text
- View/download PDF
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