Structural Basis for Selective Binding of Integrins to Extracellular Matrix

Abstract

Collagen type IV not only provides a biomechanically stable scaffold, into which the other constituents of basement membranes are incorporated, but it also plays an important role in the adhesion of cells [1,2]. This occurs mainly via α1β1 and α2β1 integrins, which are transmembrane heterodimeric glycoproteins composed of non-covalently associated α and β subunits. A non-sequential adhesion epitope for α1β1 integrin recognition, consisting of residues Arg461 of the α2(IV) chain and Asp461 of the two α1(IV) chains, has been proposed [3]. Correspondingly, the α1β1-collagen interaction has to critically depend upon the stagger of the single chains within the triple helix [4]. Although there is strong evidence for a α2α1α1′ register in natural type IV collagen [5], we have synthesized two heterotrimeric collagen peptides containing the sequence portions 457–469 of the α1 and α2 chain of type IV collagen which were regioselectively assembled via an artificial C-terminal cystine knot into the α2α1α1′ and α1α2α1′ stagger.