Elsevier

Blood Reviews

Volume 3, Issue 3, September 1989, Pages 180-191
Blood Reviews

Factor VIII structure and function

https://doi.org/10.1016/0268-960X(89)90015-5Get rights and content

Abstract

The relatively recent ability to obtain highly purified factor VIII (FVIII) preparations from plasma products, the cloning of the FVIII gene, and the expression of recombinant FVIII have provided the basis for significant advancements in the understanding of the structure-function relationships of FVIII. Evaluation of the molecular structure of FVIII has revealed the presence of domains of significant internal amino acid sequence homology as well as homology with similar structural domains of factor V. Specific proteolytic cleavage sites have been identified in the molecule and the use of site directed mutagenesis has identified those proteolytic cleavage sites required for the activation of FVIII. Deletion and substitution variants of FVIII as well as the precise epitope mapping of FVIII antibodies which inhibit the procoagulant function of the protein or its binding to von Willebrand factor have provided insight into the identification of regions of FVIII which are required for normal function.

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    This work was supported in part by Grants HL 15491, HL 31950 and DK 07022 from the National Institutes of Health. This is publication number 5538-BCR from the Research institute of Scripps Clinic.

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