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Cell. 2003 Jan 10;112(1):99-111.

Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation.

Author information

The Center for Blood Research, Department of Pathology, Department of Anesthesia, Department of Pediatrics, Boston, Massachusetts 02115.
Dana-Farber Cancer Institute, Department of Pediatrics, Department of Medicine, Department of Biological Chemistry, Department of Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439.
Contributed equally


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.

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