ArticleProtein science : a publication of the Protein Society2007
A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation.
Article in Protein science : a publication of the Protein Society, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 33 citations in OpenAlex.
- Structural dynamics and immunogenicity of the recombinant and outer membrane vesicle-embedded Meningococcal antigen NadA.Nature communications · 2026Article
- A systematic approach for evaluating the role of surface-exposed loops in trypsin-like serine proteases applied to the 170 loop in coagulation factor VIIa.Scientific reports · 2022Article
- Uncovering Membrane-Bound Models of Coagulation Factors by Combined Experimental and Computational Approaches.Thrombosis and haemostasis · 2021Review
- Evolutionary conservation of the allosteric activation of factor VIIa by tissue factor in lamprey.Journal of thrombosis and haemostasis : JTH · 2018Article
- Engineering of a membrane-triggered activity switch in coagulation factor VIIa.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity.The Journal of biological chemistry · 2016Article
- Structure-Function Relationship of the Interaction between Tissue Factor and Factor VIIa.Seminars in thrombosis and hemostasis · 2015Review
- Sites involved in intra- and interdomain allostery associated with the activation of factor VIIa pinpointed by hydrogen-deuterium exchange and electron transfer dissociation mass spectrometry.The Journal of biological chemistry · 2014Article
- Factor VII levels, R353Q and -323P0/10 Factor VII variants, and the risk of acute coronary syndrome among Arab-African Tunisians.Molecular biology reports · 2013Article
- Antibody-induced enhancement of factor VIIa activity through distinct allosteric pathways.The Journal of biological chemistry · 2012Article
- The utility of hydrogen/deuterium exchange mass spectrometry in biopharmaceutical comparability studies.Journal of pharmaceutical sciences · 2011Article
- Dynamical view of membrane binding and complex formation of human factor VIIa and tissue factor.Journal of thrombosis and haemostasis : JTH · 2010Article
- Folding and assembly of large macromolecular complexes monitored by hydrogen-deuterium exchange and mass spectrometry.Microbial cell factories · 2008Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation loop 3 (residues 365-374{216-225}) of the so-called activation domain and the 170-loop (residues 313-322{170A-175}) succeeding the TF-binding helix. The latter finding is corroborated by experiments demonstrating rapid deglycosylation of Asn322 in free FVIIa by PNGase F but almost complete protection in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural stability of activation loop 3. Altogether, our findings strongly support an allosteric activation mechanism initiated by the stabilization of the Leu305{163}/Phe374{225} pair, which, in turn, stabilizes activation loop 3 and the S(1) and S(3) substrate pockets, the activation pocket, and N-terminal insertion.
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