Coming to grips with integrin binding to ligands.
Integrins are alphabeta heterodimeric cell-surface receptors that are vital to the survival and function of nucleated cells. They recognize aspartic-acid- or a glutamic-acid-based sequence motifs in structurally diverse ligands. Integrin recognition of most ligands is divalent cation dependent and conformationally sensitive. In addition to this common property, there is an underlying binding specificity between integrins and ligands for which there has been no structural basis. The recently reported crystal structures of the extracellular segment of an integrin in its unliganded state and in complex with a prototypical Arg-Gly-Asp (RGD) ligand have provided an atomic basis for cation-mediated binding of aspartic-acid-based ligands to integrins. They also serve as a basis for modelling other integrins in complex with larger physiologic ligands. These models provide new insights into the molecular basis for ligand binding specificity in integrins and its regulation by activation-driven tertiary and quaternary changes.
Arnaout
M Amin
MA
Renal Unit, Leukocyte Biology and Inflammation Program, Massachusetts General Hospital, and Harvard Medical School, Charlestown, MA 02129, USA. arnaout@receptor.mgh.harvard.edu
Goodman
Simon L
SL
Xiong
Jian-Ping
JP
D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D002412:Cations; D019281:Dimerization; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
D002412:Cations; D039302:Integrin alphaVbeta3; D016023:Integrins; D008024:Ligands; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid