Format

Send to

Choose Destination
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

1
The Center for Blood Research, Department of Pathology, Department of Anesthesia, Department of Pediatrics, Boston, Massachusetts 02115.
2
Dana-Farber Cancer Institute, Department of Pediatrics, Department of Medicine, Department of Biological Chemistry, Department of Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
3
Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439.
#
Contributed equally

Abstract

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.

PMID:
12526797
PMCID:
PMC4372089
DOI:
10.1016/s0092-8674(02)01257-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center