Abstract

We have determined the high resolution crystal structure of the A domain from the a chain of integrin CR3. The domain adopts a classic α/β “Rossmann” fold and contains an unusual Mg 2+ coordination site at its surface. One of the coordinating ligands is the glutamate side chain from another A domain molecule. We suggest that this site represents a general metal ion-dependent adhesion site (MIDAS) for binding protein ligands. We further propose that the subunits of integrins contain a MIDAS motif within a modified A domain. Our crystal structure will allow reliable models to be built for other members of the A domain superfamily and should facilitate development of novel adhesion modulatory drugs.

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