title: Stability of a Recently Found Triple-β-Stranded Aβ1-42 Fibril Motif.
abstract: Amyloid-β peptides form polymorphous amyloid fibrils are correlated with the pathogenesis of Alzheimer's disease. Recently, a new ssNMR high-resolution structure has been reported for wild-type Aβ1-42 fibrils that is characterized by a strand-turn-strand-turn-strand motif instead of the U-shape form seen in previously known wild-type Aβ-fibril structures. Analyzing molecular dynamics simulations we comment on the relative weight of the new fibril structure and present evidence that its stability depends on hydrophobic contacts involving the C-terminal residues I41 and A42, but not on the salt bridge K28-A42. We further argue that Aβ1-42 peptides with this structure may assemble in fibrils with a 2-fold packing symmetry and discuss two possible arrangements.
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Xi
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Abbott
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Ulrich H E
authors.initials: UH
authors.lastname: Hansmann
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013696:Temperature
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)