Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18).
We have determined the high resolution crystal structure of the A domain from the alpha chain of integrin CR3. The domain adopts a classic alpha/beta "Rossmann" fold and contains an unusual Mg2+ 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 beta 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.
Lee
J O
JO
Laboratory of X-Ray Crystallography, Dana Farber Cancer Institute, Harvard Medical School Boston, Massachusetts 02115.
Rieu
P
P
Arnaout
M A
MA
Liddington
R
R
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D005340:Fibrinogen / Q000378:metabolism; D016023:Integrins / Q000737:chemistry* / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
D016023:Integrins; D016177:Macrophage-1 Antigen; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; D008274:Magnesium