Synthetic heterotrimeric collagen peptides as mimics of cell adhesion sites of the basement membrane.
Collagen type IV forms a network in the basement membrane into which other constituents of the tissue are incorporated. It also provides cell-adhesion sites that are specifically recognized by cell-surface receptors, i.e., the integrins. Different from the ubiquitous sequential RGD adhesion motif found in most of the matrix proteins, in collagen type IV, the responsible binding sites for alpha1beta1 integrin have been identified as Asp461 of the two alpha1 chains and Arg461 of the alpha2 chain. Because of the heterotrimeric character of this collagen, the spatial geometry of the binding epitope depends not only on the triple-helical fold, but decisively even on the stagger of the chains. To investigate the effects of chain registration on the conformational properties and binding affinities of this adhesion epitope, two synthetic heterotrimeric collagen peptides consisting of the identical three chains were assembled by an artificial cystine knot in two different registers, i.e., in the most plausible alpha2alpha1alpha1' and less probable alpha1alpha2alpha1' chain alignment. A detailed conformational characterization of both trimers allowed to correlate their different binding affinities for alpha1beta1 integrin with the degree of local plasticity of the two different triple helices. Optimal local breathing of the rod-shaped collagens is apparently crucial for selective recognition by proteins interacting with these main components of the extracellular matrix.
Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Christian
C
Renner
Barbara
B
Saccà
Luis
L
Moroder
D001485:Basement Membrane / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D024141:Collagen Type IV / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039423:Integrin alpha1 / Q000737:chemistry / Q000378:metabolism; D039222:Integrin alpha1beta1 / Q000737:chemistry / Q000378:metabolism*; D038982:Integrin alpha2beta1 / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
D024141:Collagen Type IV; D039423:Integrin alpha1; D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1