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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1887-1894. Prepublished online as a Blood First Edition Paper on May 16, 2006; DOI 10.1182/blood-2006-04-016485. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-04-016485v1 108/6/1887    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kani, S. Articles by Okumura, N. Search for Related Content PubMed PubMed Citation Articles by Kani, S. Articles by Okumura, N. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Analysis of fibrinogen variants at 387Ile shows that the side chain of 387 and the tertiary structure of the C-terminal tail are important not only for assembly and secretion of fibrinogen but also for lateral aggregation of protofibrils and XIIIa-catalyzed - dimer formation Satomi Kani, Fumiko Terasawa, Kazuyoshi Yamauchi, Minoru Tozuka, and Nobuo Okumura From the Laboratory of Clinical Chemistry, Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University and Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto; and Clinical Laboratory Center, University of Tokyo Hospital, Japan. To examine the role of fibrinogen -chain residue 387Ile in the assembly and secretion of this multichain protein, we synthesized a series of variants with substitution at 387 by Arg, Leu, Met, Ala, or Asp. Only the variant 387Asp showed impaired synthesis in the cells and very low secretion into the medium. In addition, we performed thrombin-catalyzed fibrin polymerization and factor (F) XIIIa-catalyzed cross-linking of the -chain for 4 variants. The degree of lateral aggregation of protofibrils into fibrin fibers was slightly reduced for 387Arg and Ala, and moderately reduced for 387Leu and Met. Although the FXIIIa-catalyzed cross-linking for all of the variants was slower than that for 387Ile, that of 387Arg was much more markedly impaired than that of the others. In summary, our studies demonstrated that the specific residue at 387 or the conformation of 388-411 residues, but not the length of the C tail, is critical for fibrinogen assembly and subsequent secretion. Moreover, this residue or the conformation is also important for not only the lateral aggregation of fibrin polymers but also the FXIIIa-catalyzed cross-linking of the -chain. Interestingly, our results clearly indicate that the conformations critical for these 2 functions are different from each other. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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