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