Regulatory element in fibrin triggers tension-activated transition from catch to slip bonds
Litvinov R. I., Kononova O., Zhmurov A. A., Marx K. A., Barsegov V., Thirumalai D., Weisel J. W.
Proceedings of the National Academy of Sciences of the United States of America
Vol.115, Issue34, P. 8075-8080
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1073/pnas.1802576115
Аннотация:
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
Ключевые слова:
Catch-slip bond; Fibrin polymerization; Fluctuating bottleneck; GPU computing; Interface remodeling
fibrin; calcium; fibrin; multiprotein complex; Article; binding affinity; binding site; calcium binding; catch bond; chemical bond; controlled study; crystal structure; fibrin clot; fibrin polymerization; in vivo study; molecular model; priority journal; protein domain; protein function; protein protein interaction; quantitative analysis; regulatory sequence; slip bond; structure analysis; tensile strength; chemistry; human; metabolism; Binding Sites; Calcium; Fibrin; Humans; Multiprotein Complexes
Язык текста: Английский
ISSN: 1091-6490
Litvinov R. I.
Kononova O.
Zhmurov A. A. Artem Andreevich 1983-
Marx K. A.
Barsegov V.
Thirumalai D.
Weisel J. W.
Литвинов Р. И.
Кононова О.
Жмуров А. А. Артем Андреевич 1983-
Марх К. А.
Барсегов В.
Тхирумалаи Д.
Wеисел Й. W.
Regulatory element in fibrin triggers tension-activated transition from catch to slip bonds
Текст визуальный непосредственный
Proceedings of the National Academy of Sciences of the United States of America
Proquest Academic Research Library
Vol.115, Issue34 P. 8075-8080
2018
Статья
Catch-slip bond Fibrin polymerization Fluctuating bottleneck GPU computing Interface remodeling
fibrin calcium fibrin multiprotein complex Article binding affinity binding site calcium binding catch bond chemical bond controlled study crystal structure fibrin clot fibrin polymerization in vivo study molecular model priority journal protein domain protein function protein protein interaction quantitative analysis regulatory sequence slip bond structure analysis tensile strength chemistry human metabolism Binding Sites Calcium Fibrin Humans Multiprotein Complexes
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