The regulation of integrin function by Ca(2+).
Integrins are metalloproteins whose receptor function is dependent on the interplay between Mg(2+) and Ca(2+). Although the specificity of the putative divalent cation binding sites has been poorly understood, some issues are becoming clearer and this review will focus on the more recent information. The MIDAS motif is a unique Mg(2+)/Mn(2+) binding site located in the integrin alpha subunit I domain. Divalent cation bound at this site has a structural role in coordinating the binding of ligand to the I domain containing integrins. The I-like domain of the integrin beta subunit also has a MIDAS-like motif but much less is known about its cation binding preferences. The N-terminal region of the integrin alpha subunit has been modelled as a beta-propeller, containing three or four 'EF hand' type divalent cation binding motifs for which the function is ill defined. It seems certain that most integrins have a high affinity Ca(2+) site which is critical for alphabeta heterodimer formation, but the location of this site is unknown. Finally intracellular Ca(2+) fluxes activate the Ca(2+) requiring enzyme, calpain, which regulates cluster formation of leucocyte integrins.
Leitinger
B
B
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, WC2A 3PX, London, UK.
McDowall
A
A
Stanley
P
P
Hogg
N
N
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D002413:Cations, Divalent; D020832:EF Hand Motifs; D004789:Enzyme Activation; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008274:Magnesium / Q000037:antagonists & inhibitors; D008345:Manganese / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D011487:Protein Conformation
D002413:Cations, Divalent; D016023:Integrins; D008345:Manganese; D002154:Calpain; D008274:Magnesium; D002118:Calcium