McPherson, H.R., Duval, C., Baker, S.R. et al. (10 more authors) (2021) Fibrinogen αC-subregions critically contribute blood clot fibre growth, mechanical stability, and resistance to fibrinolysis. eLife, 10. e68761. ISSN 2050-084X
Abstract
Fibrinogen is essential for blood coagulation. The C-terminus of the fibrinogen α-chain (αC-region) is composed of an αC-domain and αC-connector. Two recombinant fibrinogen variants (α390 and α220) were produced to investigate the role of subregions in modulating clot stability and resistance to lysis. The α390 variant, truncated before the αC-domain, produced clots with a denser structure and thinner fibres. In contrast, the α220 variant, truncated at the start of the αC-connector, produced clots that were porous with short, stunted fibres and visible fibre ends. These clots were mechanically weak and susceptible to lysis. Our data demonstrate differential effects for the αC-subregions in fibrin polymerisation, clot mechanical strength, and fibrinolytic susceptibility. Furthermore, we demonstrate that the αC-subregions are key for promoting longitudinal fibre growth. Together, these findings highlight critical functions of the αC-subregions in relation to clot structure and stability, with future implications for development of novel therapeutics for thrombosis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 McPherson et al. This article is distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use and redistribution provided that the original author and source are credited. |
Keywords: | cell biology; human; molecular biophysics; mouse; structural biology |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Nov 2021 12:50 |
Last Modified: | 01 Nov 2021 12:50 |
Status: | Published |
Publisher: | eLife Sciences Publications, Ltd |
Refereed: | Yes |
Identification Number: | 10.7554/elife.68761 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:179835 |