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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3971-3978. Prepublished online as a Blood First Edition Paper on August 19, 2004; DOI 10.1182/blood-2004-07-2544. This Article Full Text (PDF) Erratum (v105,p930) All Versions of this Article: 2004-07-2544v1 104/13/3971    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 Peng, Y. Articles by Lopez, J. A Search for Related Content PubMed PubMed Citation Articles by Peng, Y. Articles by Lopez, J. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 7, 2004 Accepted August 3, 2004 The 1 Helix-13 strand spanning Leu214-Val229 of platelet glycoprotein Ib facilitates the interaction with von Willebrand factor: evidence from characterization of the epitope of monoclonal antibody AP1 Yuandong Peng, Michael C Berndt, Miguel A Cruz, and Jose A Lopez* Department of Medicine, Baylor College of Medicine, Houston, TX, USA Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia * Corresponding author; email: Josel{at}bcm.tmc.edu. The glycoprotein (GP) Ib-IX-V complex mediates platelet binding to von Willebrand factor (VWF) through its largest polypeptide, GPIb. Of the many GPIb monoclonal antibodies described, AP1 is of particular interest because it blocks static VWF binding induced by two modulators, ristocetin and botrocetin, and platelet adhesion to VWF surfaces under flow. We mapped the AP1 binding site to a region encompassing Arg218-Tyr228, comprising the 1 helix and 13 strand defined by the GPIb crystal structure. AP1 binding absolutely required Arg218, Asp222, and Glu225. We evaluated the ability of cells expressing mutants of this region to bind VWF under static conditions in the presence of modulators, and to attach to and roll on a VWF matrix under flow. These data indicate that two regions within the sequence Arg218-Tyr228 have important roles in VWF binding: the 1 helix has a regulatory role and the turn and 13 strand bind VWF directly. Despite this, the only effect of a synthetic peptide corresponding to Leu214-Val229 was to slightly increase the rolling velocity of GPIb-expressing CHO cells on VWF. This region thus appears to be more important for maintaining the regional conformation of GPIb, thereby facilitating the interaction with VWF. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Mo, N. Lu, A. Padilla, J. A. Lopez, and R. Li The Transmembrane Domain of Glycoprotein Ibbeta Is Critical to Efficient Expression of Glycoprotein Ib-IX Complex in the Plasma Membrane J. Biol. Chem., August 11, 2006; 281(32): 23050 - 23059. [Abstract] [Full Text] [PDF] Y. Peng, C. N. Shrimpton, J.-f. Dong, and J. A. Lopez Gain of von Willebrand factor-binding function by mutagenesis of a species-conserved residue within the leucine-rich repeat region of platelet glycoprotein Ib{alpha} Blood, September 15, 2005; 106(6): 1982 - 1987. [Abstract] [Full Text] [PDF]

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