Few Ramachandran Angle Changes Provide Interaction Strength Increase in Aβ42 versus Aβ40 Amyloid Fibrils.
The pathology of Alzheimer's disease can ultimately be traced to the increased aggregation stability of Aβ42 peptides which possess two extra residues (Ile 41 &Ala 42) that the non-pathological strain (Aβ40) lacks. We have found Aβ42 fibrils to exhibit stronger energies in inter-chain interactions and we have also identified the cause for this increase to be the result of different Ramachandran angle values in certain residues of the Aβ42 strain compared to Aβ40. These unique angle configurations result in the peptide planes in the fibril structures to be more vertical along the fibril axis for Aβ42 which thus reduces the inter-atomic distance between interacting atoms on vicinal peptide chains thereby increasing the electrostatic interaction energies. We lastly postulate that these different Ramachandran angle values could possibly be traced to the unique conformational folding avenues sampled by the Aβ42 peptide owing to the presence of its two extra residues.
Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Oscar H
OH
Bastidas
Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Benjamin
B
Green
Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Mary
M
Sprague
Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Michael H
MH
Peters
D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry*; D066329:Protein Aggregates
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D066329:Protein Aggregates; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)