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 Mg{sup 2+} 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.
- Research Organization:
- Argonne National Laboratory (ANL)
- Sponsoring Organization:
- NIH; OUS
- DOE Contract Number:
- AC02-06CH11357
- OSTI ID:
- 961206
- Report Number(s):
- ANL/BIO/JA-45422
- Journal Information:
- Cell, Journal Name: Cell Journal Issue: 1 ; Jan. 10, 2003 Vol. 112; ISSN 0092-8674; ISSN CELLB5
- Country of Publication:
- United States
- Language:
- ENGLISH
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