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Regulatory element in fibrin triggers tension-activated transition from catch to slip bonds

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dc.contributor.author Litvinov R.
dc.contributor.author Kononova O.
dc.contributor.author Zhmurov A.
dc.contributor.author Marx K.
dc.contributor.author Barsegov V.
dc.contributor.author Thirumalai D.
dc.contributor.author Weisel J.
dc.date.accessioned 2019-01-22T20:33:31Z
dc.date.available 2019-01-22T20:33:31Z
dc.date.issued 2018
dc.identifier.issn 0027-8424
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/147704
dc.description.abstract © 2018 National Academy of Sciences. All Rights Reserved. Fibrin formation and mechanical stability are essential in thrombosis and hemostasis. To reveal how mechanical load impacts fibrin, we carried out optical trap-based single-molecule forced unbinding experiments. The strength of noncovalent A:a knob-hole bond stabilizing fibrin polymers first increases with tensile force (catch bonds) and then decreases with force when the force exceeds a critical value (slip bonds). To provide the structural basis of catch–slip-bond behavior, we analyzed crystal structures and performed molecular modeling of A:a knob-hole complex. The movable flap (residues γ295 to γ305) containing the weak calcium-binding site γ2 serves as a tension sensor. Flap dissociation from the B domain in the γ-nodule and translocation to knob ‘A’ triggers hole ‘a’ closure, resulting in the increase of binding affinity and prolonged bond lifetimes. The discovery of biphasic kinetics of knob-hole bond rupture is quantitatively explained by using a theory, formulated in terms of structural transitions in the binding pocket between the low-affinity (slip) and high-affinity (catch) states. We provide a general framework to understand the mechanical response of protein pairs capable of tension-induced remodeling of their association interface. Strengthening of the A:a knob-hole bonds at 30- to 40-pN forces might favor formation of nascent fibrin clots subject to hydrodynamic shear in vivo.
dc.relation.ispartofseries Proceedings of the National Academy of Sciences of the United States of America
dc.subject Catch-slip bond
dc.subject Fibrin polymerization
dc.subject Fluctuating bottleneck
dc.subject GPU computing
dc.subject Interface remodeling
dc.title Regulatory element in fibrin triggers tension-activated transition from catch to slip bonds
dc.type Article
dc.relation.ispartofseries-issue 34
dc.relation.ispartofseries-volume 115
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 8075
dc.source.id SCOPUS00278424-2018-115-34-SID85051795941


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  • Публикации сотрудников КФУ Scopus [24551]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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