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Updated: Jul 16, 2026
12:24
Helical Organization of Blood Coagulation Factor VIII on Lipid Nanotubes
Published on: June 3, 2014
Inhibitory sequences within the B-domain stabilize circulating factor V in an inactive state
Hua Zhu1, Raffaella Toso, Rodney M Camire
1Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
The Journal of Biological Chemistry
|March 28, 2007
Summary
Blood coagulation factor V (FV) remains inactive until thrombin cleaves its B-domain. Specific FV B-domain sequences inhibit activity, and their removal activates the cofactor.
Area of Science:
- Biochemistry
- Molecular Biology
- Hematology
Background:
- Blood coagulation factor V (FV) is a procofactor with minimal activity.
- Activation to factor Va by thrombin involves B-domain removal, but the mechanism is unclear.
Purpose of the Study:
- To elucidate the mechanism of factor V activation.
- To investigate how B-domain removal leads to cofactor activation.
Main Methods:
- Genetic manipulation of FV B-domain sequences (deletion/substitution).
- Assessing procoagulant function without proteolytic processing.
Main Results:
- Specific B-domain sequences can confer constitutive cofactor activity upon deletion or substitution.
- A conserved, basic amino acid cluster in the B-domain is linked to this constitutive activation.
- Proteolysis primarily removes inhibitory constraints imposed by the B-domain.
Conclusions:
- Discrete B-domain sequences stabilize the inactive FV procofactor state.
- Proteolytic activation of FV involves overcoming these inhibitory sequences.
- This provides novel insights into the factor V activation pathway.
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