Computational insights into the aggregation mechanism and amyloidogenic core of aortic amyloid medin polypeptide.

ABSTRACT: Medin amyloid, prevalent in the vessel walls of 97 % of individuals over 50, contributes to arterial stiffening and cerebrovascular dysfunction, yet our understanding of its aggregation mechanism remains limited. Dividing the full-length 50-amino-acid medin peptide into five 10-residue segments, we conducted individual investigations on each segment's self-assembly dynamics via microsecond-timescale atomistic discrete molecular dynamics (DMD) simulations. Our findings showed that medin_1-10 and medin_11-20 segments predominantly existed as isolated unstructured monomers, unable to form stable oligomers. Medin_31-40 exhibited moderate aggregation, forming dynamic β-sheet oligomers with frequent association and dissociation. Conversely, medin_21-30 and

SUBMITTER: Huang F 

PROVIDER: S-EPMC11588409 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature