title: Crystal structure of the alpha1beta1 integrin I-domain: insights into integrin I-domain function.
abstract: The alpha1beta1 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 alpha 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 alpha1beta1 integrin at 2.2 A resolution in the absence of divalent cations. The alpha1 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 alpha2beta1 I-domain which also mediates collagen binding. A unique feature of the alpha1 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 Ca2+, Mg2+ and Mn2+ 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.
authors.affiliation: Biogen, Inc., Cambridge, MA 02142, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nolte
authors.forename: R B
authors.initials: RB
authors.lastname: Pepinsky
authors.lastname: Venyaminov SYu
authors.forename: V
authors.initials: V
authors.lastname: Koteliansky
authors.forename: P J
authors.initials: PJ
authors.lastname: Gotwals
authors.forename: M
authors.initials: M
authors.lastname: Karpusas
mesh_terms: D000818:Animals; D001665:Binding Sites; D002413:Cations, Divalent; D003196:Computer Graphics; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D039222:Integrin alpha1beta1; D016023:Integrins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D002413:Cations, Divalent; D039222:Integrin alpha1beta1; D016023:Integrins; D011994:Recombinant Proteins