Biochemistry
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The broad recognition specificity exhibited by integrin α(M)β2 (Mac-1, CD11b/CD18) has allowed this adhesion receptor to play innumerable roles in leukocyte biology, yet we know little about how and why α(M)β2 binds its multiple ligands. Within α(M)β2, the α(M)I-domain is responsible for integrin's multiligand binding properties. To identify its recognition motif, we screened peptide libraries spanning sequences of many known protein ligands for α(M)I-domain binding and also selected the α(M)I-domain recognition sequences by phage display. ⋯ This prediction has been tested by examining the interaction of α(M)β2 with the human cathelicidin peptide LL-37. LL-37 induced a potent α(M)β2-dependent cell migratory response and caused activation of α(M)β2 on neutrophils. The newly revealed recognition specificity of α(M)β2 toward unfolded protein segments and cationic proteins and peptides suggests that α(M)β2 may serve as a previously proposed "alarmin" receptor with important roles in innate host defense.