Keywords: Amyloid Structure, Molecular Dynamics, Prion Hydration, Prion Protein, Steric Zipper, Serylasparaginylglutaminylasparaginylasparaginylphenylalanine, Unclassified Drug, Article, Crystal Structure, Molecular Size, Point Mutation, Prion Disease, Priority Journal, Protein Aggregation, Protein Folding, Protein Stability, Protein Structure, Simulation, Binding Sites, Computer Simulation, Dimerization, Models, Chemical, Protein Binding, Protein Conformation,
Affiliations: *** IBB - CNR ***
Istituto di Bioimmagini e Biostrutture, C.N.R., via Mezzocannone 16, I-80134 Napoli, Italy.
Dipartimento delle Scienze Biologiche, Università degli Studi di Napoli Federico II, I-80134 Napoli, Italy
References: Not available.
Structure, dynamics, and stability of assemblies of the human prion fragment SNQNNF
Misfolding of the prion protein (PrP) is associated with the development of Transmissible Spongiform Encephalopathies. The recent crystal structure of 'steric zipper' aggregates of the peptide SNQNNF (human PrP fragment 170-175) has highlighted its potential involvement in the misfolding process. A detailed molecular dynamics investigation on SNQNNF aggregates has been performed to analyze the behavior of the assemblies in a non-crystalline context. Stability, dynamics, and structural features suggest that SNQNNF assemblies are very good candidates to be involved in the structure of PrP fibrils. In addition, the analysis of small aggregates shows that steric zipper interfaces are able to stabilize assemblies composed of four strands per sheet. Altogether, the present findings indicate that steric zipper may play a key role in prion diseases. This suggestion is also corroborated by MD analyses of point mutations within the region 170-175.
Structure, dynamics, and stability of assemblies of the human prion fragment SNQNNF