We have shown that Mg/EGTA (5 mM Mg2+ and 1.5 mM EGTA) could effectively promote the adhesion of integrin alpha L beta(2) to its ligand ICAM-1 but could not promote that of the alpha L beta(2) to denatured BSA. In order to determine the structural differences between alpha L and alpha M that specifically contribute to Mg/EGTA sensitivity, a series of alpha L/alpha M chimeras were constructed. Our results showed that alpha L beta(2) with alpha M calf-1 domain completely lost the response to Mg/EGTA activation. In the reverse experiment, alpha L beta(2) would require the presence of both the alpha L calf-1 and calf-2 domain to initiate the Mg/EGTA sensitivity. (C) 2015 Elsevier Inc. All rights reserved.