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Structure-function analysis of Arg-Gly-Asp helix motifs in alpha v beta 6 integrin ligands

DiCara, Danielle, Rapisarda, Chiara, Sutcliffe, Julie L., Violette, Shelia M., Weinreb, Paul H., Hart, Ian R., Howard, Mark J., Marshall, John F. (2007) Structure-function analysis of Arg-Gly-Asp helix motifs in alpha v beta 6 integrin ligands. Journal of Biological Chemistry, 282 (13). 9657 -9665. ISSN 0021-9258. (doi:10.1074/jbc.M610461200) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1074/jbc.M610461200

Abstract

Data relating to the structural basis of ligand recognition by integrins are limited. Here we describe the physical requirements for high affinity binding of ligands to alpha v beta 6. By combining a series of structural analyses with functional testing, we show that 20-mer peptide ligands, derived from high affinity ligands of alpha v beta 6 (foot-and-mouth-disease virus, latency associated peptide), have a common structure comprising an Arg-Gly-Asp motif at the tip of a hairpin turn followed immediately by a C-terminal helix. This arrangement allows two conserved Leu/Ile residues at Asp(+1) and Asp(+4) to be presented on the outside face of the helix enabling a potential hydrophobic interaction with the alpha v beta 6 integrin, in addition to the Arg-Gly-Asp interaction. The extent of the helix determines peptide affinity for alpha v beta 6 and potency as an alpha v beta 6 antagonist. A major role of this C-terminal helix is likely to be the correct positioning of the Asp(+1) and Asp(+4) residues. These data suggest an explanation for several biological functions of alpha v beta 6 and provide a structural platform for design of alpha v beta 6 antagonists.

Item Type: Article
DOI/Identification number: 10.1074/jbc.M610461200
Subjects: Q Science > Q Science (General)
Q Science > QR Microbiology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Louise Dorman
Date Deposited: 19 Mar 2008 18:33 UTC
Last Modified: 28 May 2019 13:37 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/2346 (The current URI for this page, for reference purposes)
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