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Structure of integrin α 5 β 1 in complex with fibronectin
Author(s) -
Takagi Junichi,
Strokovich Konstantin,
Springer Timothy A.,
Walz Thomas
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg445
Subject(s) - fibronectin , integrin , biology , biophysics , protein subunit , ligand (biochemistry) , binding site , protein structure , microbiology and biotechnology , biochemistry , extracellular matrix , receptor , gene
The membrane‐distal headpiece of integrins has evolved to specifically bind large extracellular protein ligands, but the molecular architecture of the resulting complexes has not been determined. We used molecular electron microscopy to determine the three‐dimensional structure of the ligand‐binding headpiece of integrin α 5 β 1 complexed with fragments of its physiological ligand fibronectin. The density map for the unliganded α 5 β 1 headpiece shows a ‘closed’ conformation similar to that seen in the α V β 3 crystal structure. By contrast, binding to fibronectin induces an ‘open’ conformation with a dramatic, ∼80° change in the angle of the hybrid domain of the β subunit relative to its I‐like domain. The fibronectin fragment binds to the interface between the β‐propeller and I‐like domains in the integrin headpiece through the RGD‐containing module 10, but direct contact of the synergy‐region‐containing module 9 to integrin is not evident. This finding is corroborated by kinetic analysis of real‐time binding data, which shows that the synergy site greatly enhances k on but has little effect on the stability or k off of the complex.