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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1925-1932. Prepublished online as a Blood First Edition Paper on November 17, 2005; DOI 10.1182/blood-2005-10-3964. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: 2005-10-3964v1 107/5/1925    most recent Alert me when this article is cited Alert me if a correction is posted 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 Nakamura, F. Articles by Ylanne, J. Search for Related Content PubMed PubMed Citation Articles by Nakamura, F. Articles by Ylanne, J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 4, 2005 Accepted October 23, 2005 The structure of the GPIb-filamin A complex Fumihiko Nakamura, Regina Pudas, Outi Heikkinen, Perttu Permi, Ilkka Kilpelainen, Adam D Munday, John H Hartwig, Thomas P Stossel, and Jari Ylanne* Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Biocenter Oulu and Department of Biochemistry, University of Oulu, Oulu, Finland Laboratory of Organic Chemistry, Department of Chemistry, University of Helsinki, Helsinki, Finland Institute of Biotechnology, University of Helsinki, Helsinki, Finland Laboratory of Organic Chemistry, Department of Chemistry, University of Helsinki, Helsinki, Finland; Institute of Biotechnology, University of Helsinki, Helsinki, Finland Department of Biochemistry & Molecular Biology, Monash University, Clayton, Victoria, Australia Biocenter Oulu and Department of Biochemistry, University of Oulu, Oulu, Finland; Department of Biological and Environmental Science, University of Jyvaskyla, Jyvaskyla, Finland * Corresponding author; email: jylanne{at}cc.jyu.fi. Filamin A (FLNa), a dimeric actin cross-linking and scaffold protein with numerous intracellular binding partners, anchors the platelet adhesion glycoprotein (GP) Ib-IX-V receptor to actin cytoskeleton. We mapped the GPIb binding site to a single domain of FLNa and resolved the structure of this domain and its interaction complex with the corresponding GPIb cytoplasmic domain. This is the first atomic structure of this class of membrane glycoprotein-cytoskeleton connection. GPIb binds in a grove formed between the C and D strands of FLNa domain 17. The interaction is strikingly similar to that between the 7 integrin tail and a different FLNa domain, potentially defining a conserved motif for FLNa binding. Nevertheless, the structures also reveal specificity of the interfaces, which explains different regulatory mechanisms. To verify the topology of GPIb-FLNa interaction we also purified the native complex from platelets and showed that GPIb interacts with the C-terminus of FLNa, which is in accordance with our biochemical and structural data. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Filamin A interaction with GPIb: the platelet shapes up Michael C. Berndt, Susan L. Cranmer, and Robert K. Andrews Blood 2006 107: 1745. [Full Text] [PDF] This article has been cited by other articles: J. M. Beekman, C. E. van der Poel, J. A. van der Linden, D. L. C. van den Berg, P. V. E. van den Berghe, J. G. J. van de Winkel, and J. H. W. Leusen Filamin A Stabilizes Fc{gamma}RI Surface Expression and Prevents Its Lysosomal Routing J. Immunol., March 15, 2008; 180(6): 3938 - 3945. [Abstract] [Full Text] [PDF] F. Nakamura, T. M. Osborn, C. A. Hartemink, J. H. Hartwig, and T. P. Stossel Structural basis of filamin A functions J. Cell Biol., December 3, 2007; 179(5): 1011 - 1025. [Abstract] [Full Text] [PDF] A. Fontayne, B. De Maeyer, M. De Maeyer, M. Yamashita, T. Matsushita, and H. Deckmyn Paratope and Epitope Mapping of the Antithrombotic Antibody 6B4 in Complex with Platelet Glycoprotein Ib{alpha} J. Biol. Chem., August 10, 2007; 282(32): 23517 - 23524. [Abstract] [Full Text] [PDF] Y. Feng, M. H. Chen, I. P. Moskowitz, A. M. Mendonza, L. Vidali, F. Nakamura, D. J. Kwiatkowski, and C. A. Walsh Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac morphogenesis PNAS, December 26, 2006; 103(52): 19836 - 19841. [Abstract] [Full Text] [PDF]

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