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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3979-3985. Prepublished online as a Blood First Edition Paper on August 19, 2004; DOI 10.1182/blood-2004-04-1411. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1411v1 104/13/3979    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 Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Functional and structural correlations of individual IIb3 molecules Rustem I. Litvinov, Chandrasekaran Nagaswami, Gaston Vilaire, Henry Shuman, Joel S. Bennett, and John W. Weisel From the Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia; the Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia; and the Hematology-Oncology Division of the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia. The divalent cation Mn2+ and the reducing agent dithiothreitol directly shift integrins from their inactive to their active states. We used transmission electron microscopy and laser tweezers-based force spectroscopy to determine whether structural rearrangements induced by these agents in the integrin IIb3 correlate with its ability to bind fibrinogen. Mn2+ increased the probability of specific fibrinogen-IIb3 interactions nearly 20-fold in platelets, and both Mn2+ and dithiothreitol increased the probability more than 2-fold using purified proteins. Of 3 IIb3 conformations, closed with stalks touching, open with stalks separated, and globular without visible stalks, Mn2+ and dithiothreitol induced a significant increase in the proportion of open structures, as well as structural changes in the IIb3 headpiece. Mn2+ also increased the number of complexes between fibrinogen and purified IIb3 molecules, all of which were in the open conformation. Finally, Mn2+ induced the formation of IIb3 clusters that resulted from interactions exclusively involving the distal ends of the stalks. These results indicate that there is a direct correlation between IIb3 activation and the overall conformation of the molecule. Further, they are consistent with the presence of a linked equilibrium between single inactive and single active IIb3 molecules and active IIb3 clusters. (Blood. 2004;104:3979-3985) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. L. Helsten, T. A. Bunch, H. Kato, J. Yamanouchi, S. H. Choi, A. L. Jannuzi, C. C. Feral, M. H. Ginsberg, D. L. Brower, and S. J. Shattil Differences in Regulation of Drosophila and Vertebrate Integrin Affinity by Talin Mol. Biol. Cell, August 1, 2008; 19(8): 3589 - 3598. [Abstract] [Full Text] [PDF] H. Yin, R. I. Litvinov, G. Vilaire, H. Zhu, W. Li, G. A. Caputo, D. T. Moore, J. D. Lear, J. W. Weisel, W. F. DeGrado, et al. Activation of Platelet {alpha}IIbbeta3 by an Exogenous Peptide Corresponding to the Transmembrane Domain of {alpha}IIb J. Biol. Chem., December 1, 2006; 281(48): 36732 - 36741. [Abstract] [Full Text] [PDF] E. G. Arias-Salgado, F. Haj, C. Dubois, B. Moran, A. Kasirer-Friede, B. C. Furie, B. Furie, B. G. Neel, and S. J. Shattil PTP-1B is an essential positive regulator of platelet integrin signaling J. Cell Biol., August 29, 2005; 170(5): 837 - 845. [Abstract] [Full Text] [PDF] B. D. Adair, J.-P. Xiong, C. Maddock, S. L. Goodman, M. A. Arnaout, and M. Yeager Three-dimensional EM structure of the ectodomain of integrin {alpha}V{beta}3 in a complex with fibronectin J. Cell Biol., March 28, 2005; 168(7): 1109 - 1118. [Abstract] [Full Text] [PDF]

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