Missing regions within the molecular architecture of human fibrin clots structurally resolved by XL-MS and integrative structural modeling.

ABSTRACT: Upon activation, fibrinogen forms large fibrin biopolymers that coalesce into clots which assist in wound healing. Limited insights into their molecular architecture, due to the sheer size and the insoluble character of fibrin clots, have restricted our ability to develop novel treatments for clotting diseases. The, so far resolved, disparate structural details have provided insights into linear elongation; however, molecular details like the C-terminal domain of the α-chain, the heparin-binding domain on the β-chain, and other functional domains remain elusive. To illuminate these dark areas, we applied cross-linking mass spectrometry (XL-MS) to obtain biochemical evidence in the form of over 300 distance constraints and combined this with structural modeling. These restraints additionall

SUBMITTER: Klykov O 

PROVIDER: S-EPMC6995014 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature