Elucidating the Mechanism of Recognition and Binding of Heparin to Amyloid Fibrils of Serum Amyloid A.

ABSTRACT: Amyloid diseases feature pathologic deposition of normally soluble proteins and peptides as insoluble fibrils in vital organs. Amyloid fibrils co-deposit with various nonfibrillar components including heparan sulfate (HS), a glycosaminoglycan that promotes amyloid formation in vitro for many unrelated proteins. HS-amyloid interactions have been proposed as a therapeutic target for inflammation-linked amyloidosis wherein N-terminal fragments of serum amyloid A (SAA) protein deposit in the kidney and liver. The structural basis for these interactions is unclear. Here, we exploit the high-resolution cryoelectron microscopy (cryo-EM) structures of ex vivo murine and human SAA fibrils in a computational study employing molecular docking, Brownian dynamics simulations, and molecular dynamics sim

SUBMITTER: Abraham CB 

PROVIDER: S-EPMC12574783 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature