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Single-stranded, positive-sense RNA ((+)RNA) viruses replicate their genomes in virus-induced intracellular membrane compartments. (+)RNA viruses dedicate a significant part of their small genomes (a few thousands to a few tens of thousands of bases) to the generation of these compartments by encoding membrane-interacting proteins and/or protein domains. Noroviruses are a very diverse genus of (+)RNA viruses including human and animal pathogens. Human noroviruses are the major cause of acute gastroenteritis worldwide, with genogroup II genotype 4 (GII.4) noroviruses accounting for the vast majority of infections. Three viral proteins encoded in the N terminus of the viral replication polyprotein direct intracellular membrane rearrangements associated with norovirus replication. Of these three, nonstructural protein 4 (NS4) seems to be the most important, although its exact functions in replication organelle formation are unknown. Here, we produce, purify, and characterize GII.4 NS4. AlphaFold modeling combined with experimental data refines and corrects our previous crude structural model of NS4. Using simple artificial liposomes, we report an extensive characterization of the membrane properties of NS4. We find that NS4 self-assembles and thereby bridges liposomes together. Cryo-EM, NMR, and membrane flotation show formation of several distinct NS4 assemblies, at least two of them bridging pairs of membranes together in different fashions. Noroviruses belong to (+)RNA viruses whose replication compartment is extruded from the target endomembrane and generates double-membrane vesicles. Our data establish that the 21-kDa GII.4 human norovirus NS4 can, in the absence of any other factor, recapitulate in tubo several features, including membrane apposition, that occur in such processes., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Functional and versatile nano- and microassemblies formed by biological molecules are found at all levels of life, from cell organelles to full organisms. Understanding the chemical and physicochemical determinants guiding the formation of these assemblies is crucial not only to understand the biological processes they carry out but also to mimic nature. Among the synthetic peptides forming well-defined nanostructures, the octapeptide Lanreotide has been considered one of the best characterized, in terms of both the atomic structure and its self-assembly process. In the present work, we determined the atomic structure of Lanreotide nanotubes at 2.5-Å resolution by cryoelectron microscopy (cryo-EM). Surprisingly, the asymmetric unit in the nanotube contains eight copies of the peptide, forming two tetramers. There are thus eight different environments for the peptide, and eight different conformations in the nanotube. The structure built from the cryo-EM map is strikingly different from the molecular model, largely based on X-ray fiber diffraction, proposed 20 y ago. Comparison of the nanotube with a crystal structure at 0.83-Å resolution of a Lanreotide derivative highlights the polymorphism for this peptide family. This work shows once again that higher-order assemblies formed by even well-characterized small peptides are very difficult to predict., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

An understanding of the conditions that govern the self-assembly process of peptides is a fundamental step toward the design of new nanostructures that possess interesting properties. In this work, we first synthesize and explore extensively diphenylalanine (FF) self-assembling crystals formed in different solvents (i.e., solvatomorphs) using polarized optical microscopy and transmission electron microscopy. Then, we develop a numerical method that allows an unambiguous classification of the solvatomorphs through a K-means automatic clustering method. In addition, we generate a two-dimensional (2D) representation of the solvatomorphic space together with the clustering results via a principal component analysis (PCA). The classification is based on structural similarities of solvatomorphs as revealed by the analysis of their respective infrared spectra. Among the 20 samples considered, 4 clear clusters are extracted within which the compounds show very similar crystalline structures. The information extracted allows us to assign many of the peaks that appear in the complex IR spectra of the samples considered. The implementation of the overall procedure we propose, i.e., "GAULOIS" and "REFRACT-R", is transferable to other types of spectra and paves the way for a systematic, fast, and accurate classification method applicable to various types of experimental spectroscopic data.

The plastid terminal oxidase (PTOX) is a plastohydroquinone:oxygen oxidoreductase that shares structural similarities with alternative oxidases (AOXs). Multiple roles have been attributed to PTOX, such as involvement in carotene desaturation, a safety valve function, participation in the processes of chlororespiration, and setting the redox poise for cyclic electron transport. PTOX activity has been previously shown to depend on its localization at the thylakoid membrane. Here we investigate the dynamics of PTOX localization dependent on the proton motive force. Infiltrating illuminated leaves with uncouplers led to a partial dissociation of PTOX from the thylakoid membrane. In vitro reconstitution experiments showed that the attachment of purified recombinant maltose-binding protein (MBP)-OsPTOX to liposomes and isolated thylakoid membranes was strongest at slightly alkaline pH values in the presence of lower millimolar concentrations of KCl or MgCl2. In Arabidopsis thaliana overexpressing green fluorescent protein (GFP)-PTOX, confocal microscopy images showed that PTOX formed distinct spots in chloroplasts of dark-adapted or uncoupler-treated leaves, while the protein was more equally distributed in a network-like structure in the light. We propose a dynamic PTOX association with the thylakoid membrane depending on the presence of a proton motive force., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

An important aspect of cells is their shape flexibility that gives them motion but also a high adaptation versatility to their environment. This shape versatility is mediated by different types of protein-membrane interactions among which electrostatic plays an important role. In the present work we examined the interaction between a small dicationic peptide, that possesses self-assembly properties, and lipid model membranes. The peptide, lanreotide, spontaneously forms nanotubes in water that have a strictly uniform diameter. In the current work, we show that the interaction between the cationic peptide and negatively charged bilayers of lipids induces the formation of myelin sheath-like structures that we call nanoscrolls. By deciphering the different steps of formation and the molecular structure of the self-assembly, we show how electrostatics modify the spontaneous peptide and lipid way of packing.

External stimuli are powerful tools that naturally control protein assemblies and functions. For example, during viral entry and exit changes in pH are known to trigger large protein conformational changes. However, the molecular features stabilizing the higher pH structures remain unclear. Here we elucidate the conformational change of a self-assembling peptide that forms either small or large nanotubes dependent on the pH. The sub-angstrom high-pH peptide structure reveals a globular conformation stabilized through a strong histidine-serine H-bond and a tight histidine-aromatic packing. Lowering the pH induces histidine protonation, disrupts these interactions and triggers a large change to an extended β-sheet-based conformation. Re-visiting available structures of proteins with pH-dependent conformations reveals both histidine-containing aromatic pockets and histidine-serine proximity as key motifs in higher pH structures. The mechanism discovered in this study may thus be generally used by pH-dependent proteins and opens new prospects in the field of nanomaterials.

The majority of known bacteriophages have long tails that serve for bacterial target recognition and viral DNA delivery into the host. These structures form a tube from the viral capsid to the bacterial cell. The tube is formed primarily by a helical array of tail tube protein (TTP) subunits. In phages with a contractile tail, the TTP tube is surrounded by a sheath structure. Here, we report the first evidence that a phage TTP, gp17.1 of siphophage SPP1, self-assembles into long tubes in the absence of other viral proteins. gp17.1 does not exhibit a stable globular structure when monomeric in solution, even if it was confidently predicted to adopt the β-sandwich fold of phage λ TTP. However, Fourier transform infrared and nuclear magnetic resonance spectroscopy analyses showed that its β-sheet content increases significantly during tube assembly, suggesting that gp17.1 acquires a stable β-sandwich fold only after self-assembly. EM analyses revealed that the tube is formed by hexameric rings stacked helicoidally with the same organization and helical parameters found for the tail of SPP1 virions. These parameters were used to build a pseudo-atomic model of the TTP tube. The large loop spanning residues 40-56 is located on the inner surface of the tube, at the interface between adjacent monomers and hexamers. In line with our structural predictions, deletion of this loop hinders gp17.1 tube assembly in vitro and interferes with SPP1 tail assembly during phage particle morphogenesis in bacteria., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

In the absence of efficient crystallization methods, the molecular structures of fibrous assemblies have so far remained rather elusive. In this paper, we present a rational method to crystallize the lanreotide octapeptide by modification of a residue involved in a close contact. Indeed, we show that it is possible to modify the curvature of the lanreotide nanotubes and hence their diameter. This fine tuning leads to crystallization because the radius of curvature of the initially bidimensional peptide wall can be increased up to a point where the wall is essentially flat and a crystal is allowed to grow along a third dimension. By comparing X-ray diffraction data and Fourier transform Raman spectra, we show that the nanotubes and the crystals share similar cell parameters and molecular conformations, proving that there is indeed a structural continuum between these two morphologies. These results illustrate a novel approach to crystallization and represent the first step towards the acquisition of an Å-resolution structure of the lanreotide nanotubes β-sheet assembly., (Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.)

Self-assembled nanoarchitectures based on biological molecules are attractive because of the simplicity and versatility of the building blocks. However, size control is still a challenge. This control is only possible when a given system is deeply understood. Such is the case with the lanreotide acetate, an octapeptide salt that spontaneously forms monodisperse nanotubes when dissolved into pure water. Following a structural approach, we have in the past demonstrated the possibility to tune the diameter of these nanotubes while keeping a strict monodispersity, either by chemical modification of one precise amino acid on the peptide sequence or by changing the size of the counterions. On the basis of these previous studies, we replaced monovalent counterions by divalent ones to vary the number of walls. Indeed, in the present work, we show that lanreotide associated with a divalent counterion forms double-walled nanotubes while keeping the average diameter constant. However, the strict monodispersity of the number of walls was unexpected. We propose that the divalent counterions create an adhesion force that can drive the wall packing. This adhesion force is counterbalanced by a mechanical one that is related to the stiffness of the peptide wall. By taking into account these two opposite forces, we have built a general model that fully explains why the lanreotide nanotubes formed with divalent counterions possess two walls and not more.

The native hierarchical self-assembly process of natural somatostatin-14, a highly aromatic and charged peptide hormone involved in various inhibitory functions, was investigated mainly using vibrational spectroscopy (ATR-FTIR and Raman scattering) combined with electron microscopy. Generic kinetic features of amyloid fibrillogenesis were confirmed for the somatostatin-14 case, together with new insights into key interactions involved in the further hierarchical assembly of the somatostatin-14 nanofibrils into i) laterally associated nanofibers and ii) spherulite-like amyloid droplets resulting from the compaction of the nanofibers. In particular, the key role of aromatic side-chains in both fibrillogenesis and the association of the nanofibrils into higher order structures could be followed. It is proposed that the compaction propensity of the somatostatin-14 nanofibrils is relevant to the current hypothesis of the biological function of hormone self-assembly processes: hormone storage inside secretory granules.

The majority of bacterial viruses are bacteriophages bearing a tail that serves to recognise the bacterial surface and deliver the genome into the host cell. Infection is initiated by the irreversible interaction between the viral receptor binding protein (RBP) and a receptor at the surface of the bacterium. This interaction results ultimately in the phage DNA release in the host cytoplasm. Phage T5 infects Escherichia coli after binding of its RBP pb5 to the outer membrane ferrichrome transporter FhuA. Here, we have studied the complex formed by pb5 and FhuA by a variety of biophysical and biochemical techniques. We show that unlike RBPs of known structures, pb5 probably folds as a unique domain fulfilling both functions of binding to the host receptor and interaction with the rest of the phage. Pb5 likely binds to the domain occluding the β-barrel of FhuA as well as to external loops of the barrel. Furthermore, upon binding to FhuA, pb5 undergoes conformational changes, at the secondary and tertiary structure level that would be the key to the transmission of the signal through the tail to the capsid, triggering DNA release. This is the first structural information regarding the binding of a RBP to a proteic receptor., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Among noncovalent forces, electrostatic ones are the strongest and possess a rather long-range action. For these reasons, charges and counterions play a prominent role in self-assembly processes in water and therefore in many biological systems. However, the complexity of the biological media often hinders a detailed understanding of all the electrostatic-related events. In this context, we have studied the role of charges and counterions in the self-assembly of lanreotide, a cationic octapeptide. This peptide spontaneously forms monodisperse nanotubes (NTs) above a critical concentration when solubilized in pure water. Free from any screening buffer, we assessed the interactions between the different peptide oligomers and counterions in solutions, above and below the critical assembly concentration. Our results provide explanations for the selection of a dimeric building block instead of a monomeric one. Indeed, the apparent charge of the dimers is lower than that of the monomers because of strong chemisorption. This phenomenon has two consequences: (i) the dimer-dimer interaction is less repulsive than the monomer-monomer one and (ii) the lowered charge of the dimeric building block weakens the electrostatic repulsion from the positively charged NT walls. Moreover, additional counterion condensation (physisorption) occurs on the NT wall. We furthermore show that the counterions interacting with the NTs play a structural role as they tune the NTs diameter. We demonstrate by a simple model that counterions adsorption sites located on the inner face of the NT walls are responsible for this size control., (© 2011 American Chemical Society)

Supramolecular self-assembly is an attractive pathway for bottom-up synthesis of novel nanomaterials. In particular, this approach allows the spontaneous formation of structures of well-defined shapes and monodisperse characteristic sizes. Because nanotechnology mainly relies on size-dependent physical phenomena, the control of monodispersity is required, but the possibility of tuning the size is also essential. For self-assembling systems, shape, size, and monodispersity are mainly settled by the chemical structure of the building block. Attempts to change the size notably by chemical modification usually end up with the loss of self-assembly. Here, we generated a library of 17 peptides forming nanotubes of monodisperse diameter ranging from 10 to 36 nm. A structural model taking into account close contacts explains how a modification of a few Å of a single aromatic residue induces a fourfold increase in nanotube diameter. The application of such a strategy is demonstrated by the formation of silica nanotubes of various diameters.

Nanofabrication by molecular self-assembly involves the design of molecules and self-assembly strategies so that shape and chemical complementarities drive the units to organize spontaneously into the desired structures. The power of self-assembly makes it the ubiquitous strategy of living organized matter and provides a powerful tool to chemists. However, a challenging issue in the self-assembly of complex supramolecular structures is to understand how kinetically efficient pathways emerge from the multitude of possible transition states and routes. Unfortunately, very few systems provide an intelligible structure and formation mechanism on which new models can be developed. Here, we elucidate the molecular and supramolecular self-assembly mechanism of synthetic octapeptide into nanotubes in equilibrium conditions. Their complex hierarchical self-assembly has recently been described at the mesoscopic level, and we show now that this system uniquely exhibits three assembly stages and three intermediates: (i) a peptide dimer is evidenced by both analytical centrifugation and NMR translational diffusion experiments; (ii) an open ribbon and (iii) an unstable helical ribbon are both visualized by transmission electron microscopy and characterized by small angle X-ray scattering. Interestingly, the structural features of two stable intermediates are related to the final nanotube organization as they set, respectively, the nanotube wall thickness and the final wall curvature radius. We propose that a specific self-assembly pathway is selected by the existence of such preorganized and stable intermediates so that a unique final molecular organization is kinetically favored. Our findings suggests that the rational design of oligopeptides can encode both molecular- and macro-scale morphological characteristics of their higher-order assemblies, thus opening the way to ultrahigh resolution peptide scaffold engineering.

In order to better understand the mechanism of destabilization of liposomes used as drug carriers for oral administration by bile salts, the insertion and partition of sodium taurocholate (TC) into small unilamellar vesicles (SUV) and multilayers (ML) of dipalmitoylphosphatidylcholine (DPPC) were examined by continuous turbidity analysis and DSC. Optical density was recorded during the progressive solubilisation of DPPC SUV and ML into DPPC/TC mixed micelles by varying the rate of TC addition and the temperature. The results show that the insertion and diffusion of TC in the DPPC membrane is a slow process influenced by the polymorphism of the lipid, independently of its organisation. This dynamic study mimics physiological phenomena of the digestion of liposomes. In the gastrointestinal tract, DPPC SUV would be more resistant to TC than egg phosphatidylcholine (EPC) SUV [K. Andrieux, L. Forte, S. Lesieur, M. Paternostre, M. Ollivon, C. Grabielle-Madelmont, Insertion and partition of sodium taurocholate into egg phosphatidylcholine vesicles, Pharm. Res. 21 (2004) 1505-1516] because of the lower insertion of TC into DPPC bilayer at 37 degrees C at low TC concentration in the medium (fasted conditions). At high TC concentration (postprandially or after lipid absorption), the use of DPPC to prepare liposomes will delay or reduce the liberation of a drug encapsulated into liposomes in the gastrointestinal tract. As a conclusion, the addition of DPPC appears an attractive strategy to formulate orally administered liposomes.

Most synthesized peptides are nowadays produced using solid-phase procedures. Due to cleavage and purification conditions, they are mainly obtained in the presence of trifluoroacetic acid (TFA) and, for cationic peptides, as trifluoroacetate (TF-acetate) salts. However, TF-acetate interferes with physicochemical characterizations using infrared spectroscopy and might significantly affect the in vivo studies. Thus, TF-acetate exchange by another counter-ion is often required. Up to now, the classical procedure has consisted of freeze-drying the peptide several times in the presence of an excess of a stronger acid than TFA (pKa approximately 0): generally HCl (pKa = - 7). This approach means that working at pH < 1 can induce peptide degradation. We therefore tested three different approaches to exchange the tightly bound TF-acetate counter-ion from the dicationic octapeptide lanreotide: (i) reverse-phase HPLC, (ii) ion-exchange resin, and (iii) deprotonation/reprotonation cycle of the amino groups. The first two approaches allow the partial to almost complete exchange of the TF-acetate counter-ion by another ion from an acid weaker than TFA, such as acetic acid (pKa = 4.5), and the third requires a basic solution that permits the complete removal of TF-acetate counter-ion. The efficiency of these three procedures was tested and compared by using different analytical techniques such as 19F-NMR, 1H-NMR and attenuated total reflectance Fourier transformed infrared spectroscopy (ATR FT-IR). We also show that ATR-IR can be used to monitor the TFA removal. The counter-ion exchange procedures described in this study are easy to carry out, fast, harmless and reproducible. Moreover, two of them offer the very interesting possibility of exchanging the initial TF-acetate by any other counter-ion.

Lanreotide, a synthetic, therapeutic octapeptide analog of somatostatin, self-assembles in water into perfectly hollow and monodisperse (24-nm wide) nanotubes. Lanreotide is a cyclic octapeptide that contains three aromatic residues. The molecular packing of the peptide in the walls of a nanotube has recently been characterized, indicating four hierarchical levels of organization. This is a fascinating example of spontaneous self-organization, very similar to the formation of the gas vesicle walls of Halobacterium halobium. However, this unique peptide self-assembly raises important questions about its molecular origin. We adopted a directed mutation approach to determine the molecular parameters driving the formation of such a remarkable peptide architecture. We have modified the conformation by opening the cycle and by changing the conformation of a Lys residue, and we have also mutated the aromatic side chains of the peptide. We show that three parameters are essential for the formation of lanreotide nanotubes: i), the specificity of two of the three aromatic side chains, ii), the spatial arrangement of the hydrophilic and hydrophobic residues, and iii), the aromatic side chain in the beta-turn of the molecule. When these molecular characteristics are modified, either the peptides lose their self-assembling capability or they form less-ordered architectures, such as amyloid fibers and curved lamellae. Thus we have determined key elements of the molecular origins of lanreotide nanotube formation.

We investigated the spectroscopic properties of the aromatic residues in a set of octapeptides with various self-assembly properties. These octapeptides are based on lanreotide, a cyclic peptide analogue of somatostatin-14 that spontaneously self-assembles into very long and monodisperse hollow nanotubes. A previous study on these lanreotide-based derivatives has shown that the disulfide bridge, the peptide hairpin conformation and the aromatic residues are involved in the self-assembly process and that modification of these properties either decreases the self-assembly propensity or modifies the molecular packing resulting in different self-assembled architectures. In this study we probed the local environment of the aromatic residues, naphthyl-alanine, tryptophan and tyrosine, by Raman and fluorescence spectroscopy, comparing nonassembled peptides at low concentrations with the self-assembled ones at high concentrations. As expected, the spectroscopic characteristics of the aromatic residues were found to be sensitive to the peptide-peptide interactions. Among the most remarkable features we could record a very unusual Raman spectrum for the tyrosine of lanreotide in relation to its propensity to form H-bonds within the assemblies. In Lanreotide nanotubes, and also in the supramolecular architectures formed by its derivatives, the tryptophan side chain is water-exposed. Finally, the low fluorescence polarization of the peptide aggregates suggests that fluorescence energy transfer occurs within the nanotubes.

Natural Somatostatin-14 is a small cyclic neuropeptide hormone with broad inhibitory effects on endocrine secretions. Here we show that natural Somatostatin-14 spontaneously self-assembles in water and in 150 mM NaCl into liquid crystalline nanofibrils, which follow characteristic structural features of amyloid fibrils. These non-covalent highly stable structures are based on the Somatostatin native backbone conformation and are formed under non-denaturing conditions. Our results support the hypothesis that self-assembly into amyloid fibrils is a generic property of the polypeptide chain under appropriate conditions. Given recent advances on the mechanisms of biological storage and sorting modes of peptide/protein hormones into secretory granules, we propose that Somatostatin-14 fibrillation could be relevant to the regulated secretion pathway of this neuropeptide hormone. Such a hypothesis is consistent with the emerging concept of the existence of non-disease related but functional amyloids.

Diatoms, shells, bones and teeth are exquisite examples of well-defined structures, arranged from nanometre to macroscopic length scale, produced by natural biomineralization using organic templates to control the growth of the inorganic phase. Although strategies mimicking Nature have partially succeeded in synthesizing human-designed bio-inorganic composite materials, our limited understanding of fundamental mechanisms has so far kept the level of hierarchical complexity found in biological organisms out of the chemists' reach. In this letter, we report on the synthesis of unprecedented double-walled silica nanotubes with monodisperse diameters that self-organize into highly ordered centimetre-sized fibres. A unique synergistic growth mechanism is elucidated by the combination of light and electron microscopy, synchrotron X-ray diffuse scattering and Raman spectroscopy. Following this growth mechanism, macroscopic bundles of nanotubules result from the kinetic cross-coupling of two molecular processes: a dynamical supramolecular self-assembly and a stabilizing silica mineralization. The feedback actions between the template growth and the inorganic deposition are driven by a mutual electrostatic neutralization. This 'dynamical template' concept can be further generalized as a rational preparation scheme for materials with well-defined multiscale architectures and also as a fundamental mechanism for growth processes in biological systems.

Purpose: To get a continuous description of the insertion and partition processes of sodium taurocholate (TC) into the lipid bilayers of vesicles that can serve as a model for understanding the mechanism of destabilization by the bile salts of liposomes used as drug carriers for oral administration., Methods: The progressive solubilization of egg phosphatidylcholine vesicles during TC addition at controlled rates was followed by continuous turbidity (OD) and resonance energy transfer (RET) between two fluorescent probes. The influence of the lipid and TC concentrations as well as the rate of TC addition on the processes were examined., Results: Continuous turbidity recordings allowed following of the size and composition evolutions of the mixed TC/lipid aggregates formed at different steps of the vesicle-micelle transition. The solubilization mechanism is governed by complex kinetics that depend on the surfactant concentration and its addition rate. A two-step process characterizes the evolution of the vesicular state: interaction of TC molecules with the external monolayer of the vesicles first occurs. The homogeneous distribution of TC within the lipid matrix after its insertion is a very slow process. A micellar structural reorganization is observed when TC is added rapidly., Conclusions: This work provides detailed information on the slow insertion and diffusion kinetics of TC in liposomal bilayers by using a dynamic study which mimics physiological phenomena of digestion.

The binding of horse heart cytochrome c (cyt-c) and Thermus thermophilus cytochrome c(552) (cyt-c(552)) to dioleoyl phosphatidylglycerol (DOPG) vesicles was investigated using Fourier transform infrared (FTIR) spectroscopy and turbidity measurements. FTIR spectra revealed that the tertiary structures of both cytochromes became more open when bound to DOPG vesicles, but this was more pronounced for cyt-c. Their secondary structures were unchanged. Turbidity measurements showed important differences in their behavior bound to the negatively charged DOPG vesicles. Both cytochromes caused the liposomes to aggregate and flocculate, but the ways they did so differed. For cyt-c, more than a monolayer was adsorbed onto the liposome surface prior to aggregation due to charge neutralization, whereas cyt c(552) caused aggregation at a protein/lipid ratio well below that required for charge neutralization. Therefore, although cyt-c may cause liposomes to aggregate by electrostatic interaction, cyt-c(552) does not act in this way. FTIR-attenuated total reflection spectroscopy (FTIR-ATR) revealed that cyt-c lost much of its secondary structure when bound to the hydrophobic surface of octadecyltrichlorosilane, whereas cyt-c(552) folds its domains into a beta-structure. This hydrophobic effect may be the key to the difference between the behaviors of the two cytochromes when bound to DOPG vesicles.

The controlled self-assembly of complex molecules into well defined hierarchical structures is a promising route for fabricating nanostructures. These nanoscale structures can be realized by naturally occurring proteins such as tobacco mosaic virus, capsid proteins, tubulin, actin, etc. Here, we report a simple alternative method based on self-assembling nanotubes formed by a synthetic therapeutic octapeptide, Lanreotide in water. We used a multidisciplinary approach involving optical and electron microscopies, vibrational spectroscopies, and small and wide angle x-ray scattering to elucidate the hierarchy of structures exhibited by this system. The results revealed the hexagonal packing of nanotubes, and high degree of monodispersity in the tube diameter (244 A) and wall thickness (approximately equal to 18 A). Moreover, the diameter is tunable by suitable modifications in the molecular structure. The self-assembly of the nanotubes occurs through the association of beta-sheets driven by amphiphilicity and a systematic aromatic/aliphatic side chain segregation. This original and simple system is a unique example for the study of complex self-assembling processes generated by de novo molecules or amyloid peptides.