Back to Search
Start Over
Backbone Dynamics of Human Parathyroid Hormone (1-34): Flexibility of the Central Region under Different Environmental Conditions
- Source :
- Biopolymers, 84 (2006): 147–160., info:cnr-pdr/source/autori:M. Scian, M. Marin, M. Bellanda, L. Tou, J.M. Alexander, M. Rosenblatt, M. Chorev, E. Peggion, and S. Mammi/titolo:Backbone Dynamics of Human Parathyroid Hormone (1-34): Flexibility of the Central Region under Different Environmental Conditions/doi:/rivista:Biopolymers (Print)/anno:2006/pagina_da:147/pagina_a:160/intervallo_pagine:147–160/volume:84
- Publication Year :
- 2006
- Publisher :
- John Wiley & Sons, etc.], [New York, etc., Stati Uniti d'America, 2006.
-
Abstract
- The presence of a stable tertiary structure in the bioactive N-terminal portion of parathyroid hormone (PTH), a major hormone in the maintenance of extracellular calcium homeostasis, is still debated. In this work, 15N relaxation parameters of the 33 backbone amides of human PTH(1–34) were determined in phosphate-buffered saline solution (PBS) and in the presence of dodecylphosphocholine (DPC) micelles. The relaxation parameters were analyzed using both the model-free formalism (G. Lipari and A. Szabo, Journal of the American Chemical Society, 1982, Vol. 104, pp. 4546–4549) and the reduced spectral density functions approach (J.-F. Lefevre, K. T. Dayie, J. W. Peng, and G. Wagner, Biochemistry, 1996, Vol. 35, pp. 2674–2686). In PBS, the region around Gly12 possesses a high degree of flexibility and the C-terminal helix is less flexible than the N-terminal one. In the presence of DPC micelles, the mobility of the entire molecule is reduced, but the stability of the N-terminal helix increases relative to the C-terminal one. A point of relatively higher mobility at residue Gly12 is still present and a new site of local mobility at residues 16–17 is generated. These results justify the lack of experimental nuclear Overhauser effect (NOE) restraints with lack of tertiary structure and support the hypothesis that, in the absence of the receptor, the relative spatial orientation of the two N- and C-terminal helices is undefined. The flexibility in the midregion of PTH(1–34), maintained in the presence of the membrane-mimetic environment, may enable the correct relative disposition of the two helices, favoring a productive interaction with the receptor. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 147–160, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
- Subjects :
- model-free formalism
Protein Conformation
Stereochemistry
Phosphorylcholine
Recombinant Fusion Proteins
Molecular Sequence Data
Biophysics
reduced spectral density
Parathyroid hormone
membrane-mimetic environment
Nuclear Overhauser effect
Buffers
Sodium Chloride
extracellular calcium homeostasis
Biochemistry
Micelle
Protein Structure, Secondary
Biomaterials
human parathyroid hormone
Escherichia coli
Humans
Molecule
Amino Acid Sequence
Receptor
Nuclear Magnetic Resonance, Biomolecular
Micelles
Glutathione Transferase
Nitrogen Isotopes
Chemistry
Organic Chemistry
General Medicine
Peptide Fragments
Protein tertiary structure
Protein Structure, Tertiary
Solutions
15N relaxation
Parathyroid Hormone
Helix
Hydrophobic and Hydrophilic Interactions
Hormone
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Biopolymers, 84 (2006): 147–160., info:cnr-pdr/source/autori:M. Scian, M. Marin, M. Bellanda, L. Tou, J.M. Alexander, M. Rosenblatt, M. Chorev, E. Peggion, and S. Mammi/titolo:Backbone Dynamics of Human Parathyroid Hormone (1-34): Flexibility of the Central Region under Different Environmental Conditions/doi:/rivista:Biopolymers (Print)/anno:2006/pagina_da:147/pagina_a:160/intervallo_pagine:147–160/volume:84
- Accession number :
- edsair.doi.dedup.....6da68d669a8b173adc40300e23ba33d4