Blood coagulation factor Va's key interactive residues and regions for prothrombinase assembly and prothrombin binding.


Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
08 2019
Historique:
received: 21 12 2018
revised: 02 05 2019
accepted: 07 05 2019
pubmed: 19 5 2019
medline: 15 7 2020
entrez: 19 5 2019
Statut: ppublish

Résumé

Blood coagulation factor Va serves an indispensable role in hemostasis as cofactor for the serine protease factor Xa. In the presence of an anionic phospholipid membrane and calcium ions, factors Va and Xa assemble into the prothrombinase complex. Following formation of the ternary complex with the macromolecular zymogen substrate prothrombin, the latter is rapidly converted into thrombin, the key regulatory enzyme of coagulation. Over the years, multiple binding sites have been identified in factor Va that play a role in the interaction of the cofactor with factor Xa, prothrombin, or the anionic phospholipid membrane surface. In this review, an overview of the currently available information on these interactive sites in factor Va is provided, and data from biochemical approaches and 3D structural protein complex models are discussed. The structural models have been generated in recent years and provide novel insights into the molecular requirements for assembly of both the prothrombinase and the ternary prothrombinase-prothrombin complexes. Integrated knowledge of functionally important regions in factor Va will allow for a better understanding of factor Va cofactor activity.

Identifiants

pubmed: 31102425
doi: 10.1111/jth.14487
pmc: PMC6851895
pii: S1538-7836(22)14309-6
doi:

Substances chimiques

Phospholipids 0
Factor Va 65522-14-7
Prothrombin 9001-26-7
Thromboplastin 9035-58-9
Factor Xa EC 3.4.21.6

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1229-1239

Informations de copyright

© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

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Auteurs

Mark Schreuder (M)

Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.

Pieter H Reitsma (PH)

Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.

Mettine H A Bos (MHA)

Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.

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Classifications MeSH