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Blood, 1 January 2007, Vol. 109, No. 1, pp. 130-138. Prepublished online as a Blood First Edition Paper on August 29, 2006; DOI 10.1182/blood-2006-07-033910. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-033910v1 109/1/130    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 Litvinov, R. I. Articles by Weisel, J. W. Search for Related Content PubMed PubMed Citation Articles by Litvinov, R. I. Articles by Weisel, J. W. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Polymerization of fibrin: direct observation and quantification of individual B:b knob-hole interactions Rustem I. Litvinov1,, Oleg V. Gorkun2, Dennis K. Galanakis3, Sergiy Yakovlev4, Leonid Medved4, Henry Shuman5, and John W. Weisel1 1 Department of Cell and Developmental Biology and 2 Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC; 3 Departments of Pathology and Medicine, School of Medicine, State University of New York, Stony Brook, NY; and 4 Center for Vascular and Inflammatory Diseases and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 5 Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA; The polymerization of fibrin occurs primarily through interactions between N-terminal A- and B-knobs, which are exposed by the cleavage of fibrinopeptides A and B, respectively, and between corresponding a- and b-holes in the - and ß-modules. Of the potential knob-hole interactions—A:a, B:b, A:b, and B:a—the first has been shown to be critical for fibrin formation, but the roles of the others have remained elusive. Using laser tweezers–based force spectroscopy, we observed and quantified individual B:b and A:b interactions. Both desA-fibrin with exposed A-knobs and desB-fibrin bearing B-knobs interacted with fragment D from the D364H fibrinogen containing b-holes but no functional a-holes. The strength of single B:b interactions was found to be 15 to 20 pN, approximately 6-fold weaker than A:a interactions. B:b binding was abrogated by B-knob mimetic peptide, the (ß15-66)2 fragment containing 2 B-knobs, and a monoclonal antibody against the ß15-21 sequence. The interaction of desB-fibrin with fragment D containing a- and b-holes produced the same forces that were insensitive to A-knob mimetic peptide, suggesting that B:a interactions were absent. These results directly demonstrate for the first time B:b binding mediated by natural B-knobs exposed in a fibrin monomer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Parastatidis, L. Thomson, A. Burke, I. Chernysh, C. Nagaswami, J. Visser, S. Stamer, D. C. Liebler, G. Koliakos, H. F. G. Heijnen, et al. Fibrinogen {beta}-Chain Tyrosine Nitration Is a Prothrombotic Risk Factor J. Biol. Chem., December 5, 2008; 283(49): 33846 - 33853. [Abstract] [Full Text] [PDF] R. Ajjan, B. C. B. Lim, K. F. Standeven, R. Harrand, S. Dolling, F. Phoenix, R. Greaves, R. H. Abou-Saleh, S. Connell, D. A. M. Smith, et al. Common variation in the C-terminal region of the fibrinogen -chain: effects on fibrin structure, fibrinolysis and clot rigidity Blood, January 15, 2008; 111(2): 643 - 650. [Abstract] [Full Text] [PDF]

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