Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Crystallography, X-Ray
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Fibrinogen / metabolism
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Integrins / chemistry*
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Integrins / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Macrophage-1 Antigen / chemistry*
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Macrophage-1 Antigen / genetics
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Macrophage-1 Antigen / metabolism
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Magnesium / metabolism
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Models, Molecular
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Molecular Sequence Data
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Peptide Fragments / chemistry*
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Peptide Fragments / genetics
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Protein Binding
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Protein Conformation
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Recombinant Fusion Proteins / chemistry
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Structure-Activity Relationship
Substances
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Integrins
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Macrophage-1 Antigen
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Peptide Fragments
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Recombinant Fusion Proteins
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Intercellular Adhesion Molecule-1
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Fibrinogen
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Magnesium