Bioengineering Coagulation Factor VIII through Ancestral Protein Reconstruction
نویسندگان
چکیده
منابع مشابه
Bioengineering of coagulation factor VIII for improved secretion.
Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation. Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure A1-A2-B-A3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of magnitude less efficient compared with other proteins of similar size compromising rec...
متن کاملBioengineering of coagulation factor VIII for efficient expression through elimination of a dispensable disulfide loop.
BACKGROUND Heterologous expression of factor VIII (FVIII) is about two to three orders of magnitude lower than similarly sized proteins. Bioengineering strategies aimed at different structural and biochemical attributes of FVIII have been successful in enhancing its expression levels. OBJECTIVE Disulfide bonds are vital to the proper folding, secretion and stability of most secretory proteins...
متن کاملHEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Bioengineering of coagulation factor VIII for improved secretion
Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation. Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure A1-A2-BA3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of magnitude less efficient compared with other proteins of similar size compromising reco...
متن کاملEnhanced biosynthesis of coagulation factor VIII through diminished engagement of the unfolded protein response.
Human and porcine coagulation factor VIII (fVIII) display a biosynthetic efficiency differential that is being exploited for the development of new protein and gene transfer-based therapies for hemophilia A. The cellular and/or molecular mechanism(s) responsible for this phenomenon have yet to be uncovered, although it has been temporally localized to post-translational biosynthetic steps. The ...
متن کاملMolecular defects in coagulation Factor VIII and their impact on Factor VIII function.
Molecular defects in Factor VIII (FVIII), such as haemophilia A-related mutations or denaturative conformational changes, may affect the stability of FVIII as well as its interactions with physiological activators, von Willebrand Factor, phospholipid, or conformationally sensitive antibodies. We summarize the contemporary assays which allow identification of impaired functional interactions of ...
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ژورنال
عنوان ژورنال: Blood
سال: 2015
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood.v126.23.123.123