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Blood, 1 November 2005, Vol. 106, No. 9, pp. 2944-2951. Prepublished online as a Blood First Edition Paper on July 5, 2005; DOI 10.1182/blood-2005-05-2039. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-05-2039v1 106/9/2944    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 Plenary Papers Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPERS Polymerization of fibrin: specificity, strength, and stability of knob-hole interactions studied at the single-molecule level Rustem I. Litvinov, Oleg V. Gorkun, Scott F. Owen, Henry Shuman, and John W. Weisel From the Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA; the Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC; and the Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA. Using laser tweezers, we measured for the first time the forces of individual knob-into-hole interactions underlying fibrin polymerization. Exposure of A-knobs in desA-fibrin or its fragment from the central part of the molecule (N-terminal disulphide knot, NDSK) resulted in strong interactions with fibrinogen or fragment D (containing only a- and b-holes), producing a binding strength of approximately 125 to 130 pN. The interactions were not present in the absence of either knobs or holes and were abrogated by a specific inhibitor of fibrin polymerization, a peptide mimic of the A-knob (GPRPam). Exposure of both the A- and B-knobs in desAB-fibrin or desAB-NDSK did not change the rupture force spectra compared with the desA molecules, and their interactions with fibrinogen remained highly sensitive to GPRPam but not to GHRPam (B-knob), suggesting that neither A:b nor B:b nor B:a contacts contributed significantly to binding strength in addition to A:a contacts. The A:a interactions had a relatively small zero-force off-rate of approximately 10–4 s–1 and tight knob-to-hole contacts characterized by a transition state distance of approximately 0.3 nm. The results demonstrate that the knob-hole binding during thrombin-induced fibrin polymerization is driven by strong, stable, and highly specific A:a bonding, whereas A:b, B:b, or B:a interactions were not detected. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Fibrin A-knob caught in the act Dennis K. Galanakis Blood 2005 106: 2933. [Full Text] [PDF] This article has been cited by other articles: I. N. Chernysh and J. W. Weisel Dynamic imaging of fibrin network formation correlated with other measures of polymerization Blood, May 15, 2008; 111(10): 4854 - 4861. [Abstract] [Full Text] [PDF] M. J. Greene and D. M. Gordon Interaction rate informs harvester ant task decisions Behav. Ecol., March 1, 2007; 18(2): 451 - 455. [Abstract] [Full Text] [PDF] R. I. Litvinov, O. V. Gorkun, D. K. Galanakis, S. Yakovlev, L. Medved, H. Shuman, and J. W. Weisel Polymerization of fibrin: direct observation and quantification of individual B:b knob-hole interactions Blood, January 1, 2007; 109(1): 130 - 138. [Abstract] [Full Text] [PDF] D. K. Galanakis Another fibrin {alpha}C scene unmasked Blood, December 1, 2005; 106(12): 3680 - 3680. [Full Text] [PDF]

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