M35 oxidation induces Abeta40-like structural and dynamical changes in Abeta42.
Oxidizing a single M35 residue of Abeta leads to delayed aggregation and reduced toxicity. To understand the molecular mechanism of this effect, we examined the structural and dynamical consequences of M35 oxidation. We found the mobility of the C-terminal residues of Abeta42 is greatly enhanced upon M35 oxidation. In contrast, methyl groups in the central hydrophobic cluster become less flexible. Taken together, we conclude that Abeta42ox undergoes Abeta40-like structural and dynamical changes, which contribute to its reduced aggregation and toxicity.
Yan
Yilin
Y
Biology Department, Center for Biotechnology and Interdisciplinary Studies, Rensselear Polytechnic Institute, Troy, New York 12180, USA.
McCallum
Scott A
SA
Wang
Chunyu
C
D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D001430:Bacteriocins; D057927:Hydrophobic and Hydrophilic Interactions; D007554:Isotopes / Q000032:analysis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011487:Protein Conformation
D016229:Amyloid beta-Peptides; D001430:Bacteriocins; D007554:Isotopes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C514464:divergicin M35, Carnobacterium divergicin M35; D010447:Peptide Hydrolases