The regulation of integrin function by Ca2+

Integrins are metalloproteins whose receptor function is dependent on the i nterplay between Mg2+ and Ca2+. Although the specificity of the putative di valent cation binding sites has been poorly understood, some issues are bec oming clearer and this review will focus on the more recent information. Th e MIDAS motif is a unique Mg2+/Mn2+ binding site located in the integrin al pha subunit I domain. Divalent cation bound at this site has a structural r ole in coordinating the binding of ligand to the I domain containing integr ins. The I-like domain of the integrin beta subunit also has a MIDAS-like m otif but much less is known about its cation binding preferences. The N-ter minal region of the integrin a subunit has been modelled as a beta -propell er, 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 Ca2+ site which is critical for alpha beta heterodime r formation, but the location of this site is unknown. Finally intracellula r Ca2+ fluxes activate the Ca2+ requiring enzyme, calpain, which regulates cluster formation of leucocyte integrins. (C) 2000 Elsevier Science B.V. Al l rights reserved.