Crystal structure of the α1β1 integrin I‐domain: insights into integrin I‐domain function

FEBS Letters

Koteliansky, Victor²  Venyaminov, Sergei Yu.¹  Nolte, Matthias²  Pepinsky, R.Blake²  Karpusas, Michael²  Gotwals, Philip J.² 

[1] Department of Biochemistry and Molecular Biology, Mayo Foundation, 200 First St. SW, Rochester, MN 55905, USA;Biogen, Inc., 14 Cambridge Center, Cambridge, MA 02142, USA

关键词: I-domain;    Integrin;    Metal binding;    Collagen;    Adhesion;    Crystal structure;   

DOI  :  10.1016/S0014-5793(99)00666-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 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.

【 授权许可】

Unknown