Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation |
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Authors: | Shimaoka Motomu Xiao Tsan Liu Jin-Huan Yang Yuting Dong Yicheng Jun Chang-Duk McCormack Alison Zhang Rongguang Joachimiak Andrzej Takagi Junichi Wang Jia-Huai Springer Timothy A |
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Affiliation: | The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. |
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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. |
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