Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2936K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Springer, T. A. Articles by Xiao, T. Search for Related Content PubMed PubMed Citation Articles by Springer, T. A. Articles by Xiao, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Social Bookmarking                            What's this?

Structural basis for distinctive recognition of fibrinogen C peptide by the platelet integrin _IIbβ₃

¹ Immune Disease Institute and ² Department of Pathology, Harvard Medical School, Boston, MA 02115

Correspondence to Timothy A. Springer: springeroffice{at}idi.harvard.edu

Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin _IIbβ₃ on platelets, resulting in platelet aggregation. _vβ₃ binds fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's subunit. _IIbβ₃ also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the subunit (C peptide). These distinct modes of fibrinogen binding enable _IIbβ₃ and _vβ₃ to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin _IIbβ₃–C peptide interface, and, for comparison, integrin _IIbβ₃ bound to a lamprey C primordial RGD motif. Compared with RGD, the GAKQAGDV motif in C adopts a different backbone configuration and binds over a more extended region. The integrin metal ion–dependent adhesion site (MIDAS) Mg²⁺ ion binds the C Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca²⁺ ion binds the C C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered C peptide enhances our understanding of the involvement of C peptide and integrin _IIbβ₃ in hemostasis and thrombosis.

Abbreviations used in this paper: ADMIDAS, adjacent to MIDAS; I-EGF, integrin EGF-like; MIDAS, metal ion–dependent adhesion site.

© 2008 Springer et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Tan, K., Duquette, M., Joachimiak, A., Lawler, J. (2009). The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, glycosaminoglycan and integrin binding. FASEB J. 23: 2490-2501 [Abstract] [Full Text]  
• Luo, B.-H., Karanicolas, J., Harmacek, L. D., Baker, D., Springer, T. A. (2009). Rationally Designed Integrin {beta}3 Mutants Stabilized in the High Affinity Conformation. J. Biol. Chem. 284: 3917-3924 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents