Cryo-EM structure of coagulation factor V short.
Research article published in Blood (2023)
Abstract
Coagulation factor V (fV) is the precursor of activated fV (fVa), an essential component of the prothrombinase complex required for the rapid activation of prothrombin in the penultimate step of the coagulation cascade. In addition, fV regulates the tissue factor pathway inhibitor α (TFPIα) and protein C pathways that inhibit the coagulation response. A recent cryogenic electron microscopy (cryo-EM) structure of fV has revealed the architecture of its A1-A2-B-A3-C1-C2 assembly but left the mechanism that keeps fV in its inactive state unresolved because of an intrinsic disorder in the B domain. A splice variant of fV, fV short, carries a large deletion of the B domain that produces constitutive fVa-like activity and unmasks epitopes for the binding of TFPIα. The cryo-EM structure of fV short was solved at 3.2 Å resolution and revealed the arrangement of the entire A1-A2-B-A3-C1-C2 assembly. The shorter B domain stretches across the entire width of the protein, making contacts with the A1, A2, and A3 domains but suspended over the C1 and C2 domains. In the portion distal to the splice site, several hydrophobic clusters and acidic residues provide a potential binding site for the basic C-terminal end of TFPIα. In fV, these epitopes may bind intramolecularly to the basic region of the B domain. The cryo-EM structure reported in this study advances our understanding of the mechanism that keeps fV in its inactive state, provides new targets for mutagenesis and facilitates future structural analysis of fV short in complex with TFPIα, protein S, and fXa.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Coagulation factor V (fV) is the precursor of activated fV (fVa), an essential component of the prothrombinase complex required for the rapid activation of prothrombin in the penultimate step of the coagulation cascade. In addition, fV regulates the tissue factor pathway inhibitor α (TFPIα) and...
Por qué esto importa para la hirudoterapia
Este estudio resolvió la estructura de criomicroscopía electrónica (cryo-EM) del factor V de coagulación corto (factor V short) a una resolución de 3,2 Å, revelando cómo las interacciones del dominio B mantienen al factor V inactivo y cómo el dominio B acortado en la variante de splicing expone epítopos para la unión del inhibidor de la vía del factor tisular α (TFPIα), produciendo una actividad constitutiva similar a la del factor Va. El trabajo avanza en la comprensión de los mecanismos reguladores de la cascada de coagulación y aporta una base estructural para futuros análisis de mutagénesis y de complejos. El resumen no menciona sanguijuelas, hirudoterapia, hirudina ni ningún compuesto derivado de sanguijuelas. Su relevancia para la ASH es, en el mejor de los casos, indirecta, limitada al ámbito compartido de la biología de la coagulación sanguínea sin ninguna conexión directa con las sanguijuelas.
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Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: 18 de junio de 2026