HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 46, 47763-47772, November 12, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/46/47763    most recent M404685200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siljander, P. R.-M. Articles by Farndale, R. W. Search for Related Content PubMed PubMed Citation Articles by Siljander, P. R.-M. Articles by Farndale, R. W. Social Bookmarking                      What's this?

Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens^*

Pia R.-M. Siljander, Samir Hamaia, Anthony R. Peachey, David A. Slatter, Peter A. Smethurst, Willem H. Ouwehand¶, C. Graham Knight, and Richard W. Farndale

From the Departments of Biochemistry and ^¶Haematology, University of Cambridge, Downing Site, Cambridge CB2 1QW, United Kingdom

Only three recognition motifs, GFOGER, GLOGER, and GASGER, all present in type I collagen, have been identified to date for collagen-binding integrins, such as ₂₁. Sequence alignment was used to investigate the occurrence of related motifs in other human fibrillar collagens, and located a conserved array of novel GER motifs within their triple helical domains. We compared the integrin binding properties of synthetic triple helical peptides containing examples of such sequences (GLSGER, GMOGER, GAOGER, and GQRGER) or the previously identified motifs. Recombinant inserted (I) domains of integrin subunits ₁, ₂ and ₁₁ all bound poorly to all motifs other than GFOGER and GLOGER. Similarly, ₂₁ -containing resting platelets adhered well only to GFOGER and GLOGER, while ADP-activated platelets, HT1080 cells and two active ₂I domain mutants (E318W, locked open) bound all motifs well, indicating that affinity modulation determines the sequence selectivity of integrins. GxO/SGER peptides inhibited platelet adhesion to collagen monomers with order of potency F L M > A. These results establish GFOGER as a high affinity sequence, which can interact with the ₂I domain in the absence of activation and suggest that integrin reactivity of collagens may be predicted from their GER content.

Received for publication, April 27, 2004 , and in revised form, August 13, 2004.

^* This research was supported by grants from the British Heart Foundation and Medical Research Council. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Supplementary Data.

To whom correspondence should be addressed: Dept. of Biochemistry, University of Cambridge, Main Building, Downing site, Tennis Court Rd., CB21QW Cambridge, UK. Tel.: 44-1223-766-113; Fax: 44-1223-333-345; E-mail: prms2{at}mole.bio.cam.ac.uk.

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

This article has been cited by other articles:

				M. C. Erat, D. A. Slatter, E. D. Lowe, C. J. Millard, R. W. Farndale, I. D. Campbell, and I. Vakonakis Identification and structural analysis of type I collagen sites in complex with fibronectin fragments PNAS, March 17, 2009; 106(11): 4195 - 4200. [Abstract] [Full Text] [PDF]

				E. Adiguzel, P. J Ahmad, C. Franco, and M. P Bendeck Collagens in the progression and complications of atherosclerosis Vascular Medicine, February 1, 2009; 14(1): 73 - 89. [Abstract] [PDF]

				C. C. Caswell, M. Barczyk, D. R. Keene, E. Lukomska, D. E. Gullberg, and S. Lukomski Identification of the First Prokaryotic Collagen Sequence Motif That Mediates Binding to Human Collagen Receptors, Integrins {alpha}2{beta}1 and {alpha}11{beta}1 J. Biol. Chem., December 26, 2008; 283(52): 36168 - 36175. [Abstract] [Full Text] [PDF]

				A. Gigout, M. Jolicoeur, M. Nelea, N. Raynal, R. Farndale, and M. D. Buschmann Chondrocyte Aggregation in Suspension Culture Is GFOGER-GPP- and {beta}1 Integrin-dependent J. Biol. Chem., November 14, 2008; 283(46): 31522 - 31530. [Abstract] [Full Text] [PDF]

				S. M. Sweeney, J. P. Orgel, A. Fertala, J. D. McAuliffe, K. R. Turner, G. A. Di Lullo, S. Chen, O. Antipova, S. Perumal, L. Ala-Kokko, et al. Candidate Cell and Matrix Interaction Domains on the Collagen Fibril, the Predominant Protein of Vertebrates J. Biol. Chem., July 25, 2008; 283(30): 21187 - 21197. [Abstract] [Full Text] [PDF]

				C. Giudici, N. Raynal, H. Wiedemann, W. A. Cabral, J. C. Marini, R. Timpl, H. P. Bachinger, R. W. Farndale, T. Sasaki, and R. Tenni Mapping of SPARC/BM-40/Osteonectin-binding Sites on Fibrillar Collagens J. Biol. Chem., July 11, 2008; 283(28): 19551 - 19560. [Abstract] [Full Text] [PDF]

				G. E. Jarvis, N. Raynal, J. P. Langford, D. J. Onley, A. Andrews, P. A. Smethurst, and R. W. Farndale Identification of a major GpVI-binding locus in human type III collagen Blood, May 15, 2008; 111(10): 4986 - 4996. [Abstract] [Full Text] [PDF]

				A. D. Konitsiotis, N. Raynal, D. Bihan, E. Hohenester, R. W. Farndale, and B. Leitinger Characterization of High Affinity Binding Motifs for the Discoidin Domain Receptor DDR2 in Collagen J. Biol. Chem., March 14, 2008; 283(11): 6861 - 6868. [Abstract] [Full Text] [PDF]

				T. Koide Designed triple-helical peptides as tools for collagen biochemistry and matrix engineering Phil Trans R Soc B, August 29, 2007; 362(1484): 1281 - 1291. [Abstract] [Full Text] [PDF]

				N. J. Turner, M. O. Murphy, C. M. Kielty, C. A. Shuttleworth, R. A. Black, M. J. Humphries, M. G. Walker, and A. E. Canfield {alpha}2(VIII) Collagen Substrata Enhance Endothelial Cell Retention Under Acute Shear Stress Flow via an {alpha}2{beta}1 Integrin-Dependent Mechanism: An In Vitro and In Vivo Study Circulation, August 22, 2006; 114(8): 820 - 829. [Abstract] [Full Text] [PDF]

				N. Raynal, S. W. Hamaia, P. R.-M. Siljander, B. Maddox, A. R. Peachey, R. Fernandez, L. J. Foley, D. A. Slatter, G. E. Jarvis, and R. W. Farndale Use of Synthetic Peptides to Locate Novel Integrin {alpha}2beta1-binding Motifs in Human Collagen III J. Biol. Chem., February 17, 2006; 281(7): 3821 - 3831. [Abstract] [Full Text] [PDF]

				J. K. Kim, Y. Xu, X. Xu, D. R. Keene, S. Gurusiddappa, X. Liang, K. K. Wary, and M. Hook A Novel Binding Site in Collagen Type III for Integrins {alpha}1{beta}1 and {alpha}2{beta}1 J. Biol. Chem., September 16, 2005; 280(37): 32512 - 32520. [Abstract] [Full Text] [PDF]

				S. Penz, A. J. Reininger, R. Brandl, P. Goyal, T. Rabie, I. Bernlochner, E. Rother, C. Goetz, B. Engelmann, P. A. Smethurst, et al. Human atheromatous plaques stimulate thrombus formation by activating platelet glycoprotein VI FASEB J, June 1, 2005; 19(8): 898 - 909. [Abstract] [Full Text] [PDF]

				J. O. Humtsoe, J. K. Kim, Y. Xu, D. R. Keene, M. Hook, S. Lukomski, and K. K. Wary A Streptococcal Collagen-like Protein Interacts with the {alpha}2{beta}1 Integrin and Induces Intracellular Signaling J. Biol. Chem., April 8, 2005; 280(14): 13848 - 13857. [Abstract] [Full Text] [PDF]

				J. Kapyla, J. Jaalinoja, M. Tulla, J. Ylostalo, L. Nissinen, T. Viitasalo, P. Vehvilainen, V. Marjomaki, P. Nykvist, A.-M. Saamanen, et al. The Fibril-associated Collagen IX Provides a Novel Mechanism for Cell Adhesion to Cartilaginous Matrix J. Biol. Chem., December 3, 2004; 279(49): 51677 - 51687. [Abstract] [Full Text] [PDF]