DiCara, D. and Rapisarda, C. and Sutcliffe, J.L. and Violette, S.M. and Weinreb, P.H. and Hart, I.R. and Howard, M.J. and Marshall, J.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 .
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| Official URL http://www.jbc.org/cgi/reprint/282/13/9657?maxtosh... |
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 |
|---|---|
| Subjects: | Q Science > Q Science (General) Q Science > QR Microbiology |
| Divisions: | Faculties > Science Technology and Medical Studies > School of Biosciences |
| Depositing User: | Louise Dorman |
| Date Deposited: | 19 Mar 2008 18:33 |
| Last Modified: | 14 Jan 2010 14:06 |
| Resource URI: | http://kar.kent.ac.uk/id/eprint/2346 (The current URI for this page, for reference purposes) |
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