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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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.
|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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