Structure-Function Analysis of Arg-Gly-Asp Helix Motifs in αvβ6 Integrin Ligands

摘要: Data relating to the structural basis of ligand recognition by integrins are limited. Here we describe physical requirements for high affinity binding ligands αvβ6. By combining a series analyses with functional testing, show that 20-mer peptide ligands, derived from αvβ6 (foot-and-mouth-disease virus, latency associated peptide), have common structure comprising an Arg-Gly-Asp motif at tip hairpin turn followed immediately C-terminal helix. This arrangement allows two conserved Leu/Ile residues Asp+1 and Asp+4 be presented on outside face helix enabling potential hydrophobic interaction integrin, in addition interaction. The extent determines potency as antagonist. A major role this is likely correct positioning residues. These data suggest explanation several biological functions provide platform design antagonists.