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Crystal structure of the α1β1 integrin I‐domain: insights into integrin I‐domain function
Author(s) -
Nolte Matthias,
Pepinsky R.Blake,
Venyaminov Sergei Yu.,
Koteliansky Victor,
Gotwals Philip J.,
Karpusas Michael
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00666-3
Subject(s) - integrin , chemistry , divalent , crystallography , binding site , ligand (biochemistry) , biophysics , crystal structure , egf like domain , binding domain , protein structure , stereochemistry , receptor , biochemistry , biology , organic chemistry
The α1β1 integrin is a major cell surface receptor for collagen. Ligand binding is mediated, in part, through a ∼200 amino acid inserted ‘I’‐domain contained in the extracellular part of the integrin α chain. Integrin I‐domains contain a divalent cation binding (MIDAS) site and require cations to interact with integrin ligands. We have determined the crystal structure of recombinant I‐domain from the rat α1β1 integrin at 2.2 Å resolution in the absence of divalent cations. The α1 I‐domain adopts the dinucleotide binding fold that is characteristic of all I‐domain structures that have been solved to date and has a structure very similar to that of the closely related α2β1 I‐domain which also mediates collagen binding. A unique feature of the α1 I‐domain crystal structure is that the MIDAS site is occupied by an arginine side chain from another I‐domain molecule in the crystal, in place of a metal ion. This interaction supports a proposed model for ligand‐induced displacement of metal ions. Circular dichroism spectra determined in the presence of Ca 2+ , Mg 2+ and Mn 2+ indicate that no changes in the structure of the I‐domain occur upon metal ion binding in solution. Metal ion binding induces small changes in UV absorption spectra, indicating a change in the polarity of the MIDAS site environment.