Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation.
The structure of the I domain of integrin alpha L beta 2 bound to the Ig superfamily ligand ICAM-1 reveals the open ligand binding conformation and the first example of an integrin-IgSF interface. The I domain Mg2+ directly coordinates Glu-34 of ICAM-1, and a dramatic swing of I domain residue ... Glu-241 enables a critical salt bridge. Liganded and unliganded structures for both high- and intermediate-affinity mutant I domains reveal that ligand binding can induce conformational change in the alpha L I domain and that allosteric signals can convert the closed conformation to intermediate or open conformations without ligand binding. Pulling down on the C-terminal alpha 7 helix with introduced disulfide bonds ratchets the beta 6-alpha 7 loop into three different positions in the closed, intermediate, and open conformations, with a progressive increase in affinity.
Mesh Terms:
Amino Acid Substitution, Animals, Cells, Cultured, Crystallography, X-Ray, Disulfides, Escherichia coli, Glutamine, Integrins, Intercellular Adhesion Molecule-1, Ligands, Lymphocyte Function-Associated Antigen-1, Magnesium, Models, Molecular, Molecular Conformation, Mutation, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Spectrum Analysis, Raman, Surface Plasmon Resonance
Amino Acid Substitution, Animals, Cells, Cultured, Crystallography, X-Ray, Disulfides, Escherichia coli, Glutamine, Integrins, Intercellular Adhesion Molecule-1, Ligands, Lymphocyte Function-Associated Antigen-1, Magnesium, Models, Molecular, Molecular Conformation, Mutation, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Spectrum Analysis, Raman, Surface Plasmon Resonance
Cell
Date: Jan. 10, 2003
PubMed ID: 12526797
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