SEARCH:   Advanced

Blood, 1 February 2008, Vol. 111, No. 3, pp. 1240-1247. Prepublished online as a Blood First Edition Paper on November 1, 2007; DOI 10.1182/blood-2007-08-109918. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-08-109918v1 blood-2007-08-109918v2 111/3/1240    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shen, B. W. Articles by Stoddard, B. L. Search for Related Content PubMed PubMed Citation Articles by Shen, B. W. Articles by Stoddard, B. L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The tertiary structure and domain organization of coagulation factor VIII Betty W. Shen1, Paul Clint Spiegel1, Chong-Hwan Chang2, Jae-Wook Huh2, Jung-Sik Lee2, Jeanman Kim2, Young-Ho Kim3, and Barry L. Stoddard1 1 Program in Molecular Biophysics, Structure and Design, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; 2 Central Research Institute, Green Cross Corporation, Yongin, Korea; and 3 Department of Life Sciences, The University of Suwon, Kyongi-do, Korea Factor VIII (fVIII) is a serum protein in the coagulation cascade that nucleates the assembly of a membrane-bound protease complex on the surface of activated platelets at the site of a vascular injury. Hemophilia A is caused by a variety of mutations in the factor VIII gene and typically requires replacement therapy with purified protein. We have determined the structure of a fully active, recombinant form of factor VIII (r-fVIII), which consists of a heterodimer of peptides, respectively containing the A1-A2 and A3-C1-C2 domains. The structure permits unambiguous modeling of the relative orientations of the 5 domains of r-fVIII. Comparison of the structures of fVIII, fV, and ceruloplasmin indicates that the location of bound metal ions and of glycosylation, both of which are critical for domain stabilization and association, overlap at some positions but have diverged at others. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Casana, N. Cabrera, A. R. Cid, S. Haya, M. Beneyto, C. Espinos, V. Cortina, M. A. Dasi, and J. A. Aznar Severe and moderate hemophilia A: identification of 38 new genetic alterations Haematologica, July 1, 2008; 93(7): 1091 - 1094. [Abstract] [Full Text] [PDF] H. Wakabayashi and P. J. Fay Identification of Residues Contributing to A2 Domain-dependent Structural Stability in Factor VIII and Factor VIIIa J. Biol. Chem., April 25, 2008; 283(17): 11645 - 11651. [Abstract] [Full Text] [PDF] A. Vencesla, M. A. Corral-Rodriguez, M. Baena, M. Cornet, M. Domenech, M. Baiget, P. Fuentes-Prior, and E. F. Tizzano Identification of 31 novel mutations in the F8 gene in Spanish hemophilia A patients: structural analysis of 20 missense mutations suggests new intermolecular binding sites Blood, April 1, 2008; 111(7): 3468 - 3478. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020