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Model of the αLβ2 integrin I‐domain/ICAM‐1 DI interface suggests that subtle changes in loop orientation determine ligand specificity
Author(s) -
Legge Glen B.,
Morris Garrett M.,
Sanner Michel F.,
Takada Yoshikazu,
Olson Arthur J.,
Grynszpan Flavio
Publication year - 2002
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10134
Subject(s) - ligand (biochemistry) , domain (mathematical analysis) , chemistry , adhesion , integrin , biophysics , protein subunit , carboxylate , icam 1 , binding site , intercellular adhesion molecule 1 , protein structure , stereochemistry , intracellular , biochemistry , biology , receptor , mathematical analysis , mathematics , organic chemistry , gene
The interaction of the αLβ2 integrin with its cellular ligand the intercellular adhesion molecule‐1 (ICAM‐1) is critical for the tight binding interaction between most leukocytes and the vascular endothelium before transendothelial migration to the sites of inflammation. In this article we have modeled the αL subunit I‐domain in its active form, which was computationally docked with the D1 domain of the ICAM‐1 to probe potential protein‐protein interactions. The experimentally observed key interaction between the carboxylate of Glu 34 in the ICAM‐1 D1 domain and the metal ion‐dependent adhesion site (MIDAS) in the open αL I‐domain was consistently reproduced by our calculations. The calculations reveal the nature of the αLβ2/ICAM‐1 interaction and suggest an explanation for the increased ligand‐binding affinity in the “open” versus the “closed” conformation of the αL I‐domain. A mechanism for substrate selectivity among αL, αM, and α2 I‐domains is suggested whereby the orientation of the loops within the I‐domain is critical in mediating the interaction of the Glu 34 carboxylate of ICAM‐1 D1 with the MIDAS. Proteins 2002;48:151–160. © 2002 Wiley‐Liss, Inc.