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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3725-3732. Prepublished online as a Blood First Edition Paper on January 5, 2007; DOI 10.1182/blood-2006-11-058420. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-11-058420v1 109/9/3725    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 Beau Mitchell, W. Articles by Coller, B. S. Search for Related Content PubMed PubMed Citation Articles by Beau Mitchell, W. Articles by Coller, B. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Mapping early conformational changes in IIb and ß3 during biogenesis reveals a potential mechanism for IIbß3 adopting its bent conformation W. Beau Mitchell1,2, Jihong Li2, Marta Murcia2,3, Nathalie Valentin4, Peter J. Newman5, and Barry S. Coller2 1 Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; 2 Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY; 3 Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY; 4 Laboratoire d'Immunologie, Centre Hospitalier Universitaire, Nantes, France; 5 Blood Center of Wisconsin, Milwaukee, WI Current evidence supports a model in which the low-affinity state of the platelet integrin IIbß3 results from IIbß3 adopting a bent conformation. To assess IIbß3 biogenesis and how IIbß3 initially adopts the bent conformation, we mapped the conformational states occupied by IIb and ß3 during biogenesis using conformation-specific monoclonal antibodies (mAbs). We found that IIbß3 complex formation was not limited by the availability of either free pro-IIb or free ß3, suggesting that other molecules, perhaps chaperones, control complex formation. Five ß3-specific, ligand-induced binding site (LIBS) mAbs reacted with much or all free ß3 but not with ß3 when in complex with mature IIb, suggesting that ß3 adopts its mature conformation only after complex formation. Conversely, 2 IIb-specific LIBS mAbs directed against the IIb Calf-2 region adjacent to the membrane reacted with only minor fractions of free pro-IIb, raising the possibility that pro-IIb adopts a bent conformation early in biogenesis. Our data suggest a working model in which pro-IIb adopts a bent conformation soon after synthesis, and then ß3 assumes its bent conformation by virtue of its interaction with the bent pro-IIb. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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