Atomic Structural Models of Fibrin Oligomers

Structure
Artem ZhmurovValeri Barsegov

Abstract

The space-filling fibrin network is a major part of clots and thrombi formed in blood. Fibrin polymerization starts when fibrinogen, a plasma protein, is proteolytically converted to fibrin, which self-assembles to form double-stranded protofibrils. When reaching a critical length, these intermediate species aggregate laterally to transform into fibers arranged into branched fibrin network. We combined multiscale modeling in silico with atomic force microscopy (AFM) imaging to reconstruct complete atomic models of double-stranded fibrin protofibrils with γ-γ crosslinking, A:a and B:b knob-hole bonds, and αC regions-all important structural determinants not resolved crystallographically. Structures of fibrin oligomers and protofibrils containing up to 19 monomers were successfully validated by quantitative comparison with high-resolution AFM images. We characterized the protofibril twisting, bending, kinking, and reversibility of A:a knob-hole bonds, and calculated hydrodynamic parameters of fibrin oligomers. Atomic structures of protofibrils provide a basis to understand mechanisms of early stages of fibrin polymerization.

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Citations

Jan 12, 2020·Proceedings of the National Academy of Sciences of the United States of America·Oleg KlykovRichard A Scheltema
Mar 27, 2020·Research and Practice in Thrombosis and Haemostasis·Laura SachsRaghavendra Palankar
Apr 28, 2019·The Journal of Biological Chemistry·Lauren R SchmittKirk C Hansen
Jun 23, 2021·Colloids and Surfaces. B, Biointerfaces·Nikolay A BarinovDmitry V Klinov
Nov 11, 2021·Journal of the Royal Society, Interface·Naoki TakeishiShigeo Wada

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