title: Dynamical properties of steric zipper polymorphs formed by a IAPP-derived peptide.
abstract: Understanding the molecular basis of neurodegenerative diseases has enormous implications for the development of effective therapeutic strategies. One of the most puzzling features of these pathologies is the occurrence of distinct strains, which are believed to be generated by alternative conformational transitions of the same protein/peptide. Very recently, it has been discovered that small model peptides are able to form alternative tightly packed assemblies (polymorphs) in the crystalline state. Intriguingly, it has been postulated that the different polymorphs of the same polypeptide sequence may be representative of distinct strains. As the organization of crystalline aggregates of small peptides may be heavily biased by crystal packing, we have here performed MD simulations on steric zipper polymorphs formed by of the IAPP-derived fragment SSTNVG. Our analyses show that these aggregates are rather stable also in a non-crystalline environment. This finding corroborates the hypothesis that steric zipper assemblies are good candidates to account for the phenomenon of strain in neurodegenerative diseases. Present investigations also provide clues on the factors that favour the formation of polymorphs. Indeed, the intrinsic stability of individual β-sheets formed by SSTNVG strands is very poor. Therefore, the formation of these aggregates is essentially dictated by inter-sheet interactions established within the steric zipper assembly.
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR via Mezzocannone 16, I-80134 Napoli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Stanzione
authors.forename: Alfonso
authors.initials: A
authors.lastname: De Simone
authors.forename: Luciana
authors.initials: L
authors.lastname: Esposito
authors.forename: Luigi
authors.initials: L
authors.lastname: Vitagliano
mesh_terms: D003460:Crystallization; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D010641:Phenotype; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides