Fibrinogen function achieved through multiple covalent states

Fibrinogen function achieved through multiple covalent states.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41467-020-19295-7
Journal or Publication Title: Nature Communications
Volume: 11
Number: 1
Date: 29 October 2020
Divisions: ACRF Centenary Cancer Research Centre
Depositing User: General Admin
Identification Number: 10.1038/s41467-020-19295-7
ISSN: 2041-1723
Date Deposited: 05 Jan 2021 05:18
Abstract:

Disulfide bonds link pairs of cysteine amino acids and their formation is assumed to be complete in the mature, functional protein. Here, we test this assumption by quantifying the redox state of disulfide bonds in the blood clotting protein fibrinogen. The disulfide status of fibrinogen from healthy human donor plasma and cultured human hepatocytes are measured using differential cysteine alkylation and mass spectrometry. This analysis identifies 13 disulfide bonds that are 10-50% reduced, indicating that fibrinogen is produced in multiple disulfide-bonded or covalent states. We further show that disulfides form upon fibrin polymerization and are required for a robust fibrin matrix that withstands the mechanical forces of flowing blood and resists premature fibrinolysis. The covalent states of fibrinogen are changed by fluid shear forces ex vivo and in vivo, indicating that the different states are dynamic. These findings demonstrate that fibrinogen exists and functions as multiple covalent forms.

Creators:
Creators
Email
Butera, Diego
UNSPECIFIED
Hogg, Philip J.
UNSPECIFIED
Last Modified: 05 Jan 2021 05:18
URI: https://eprints.centenary.org.au/id/eprint/923

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