Fine structure of collagen: Molecular mechanisms of the interactions of collagen

摘要

Collagen is a multifunctional protein which enters into highly specific interactions with many proteins including cell surface receptors. The physiological solid state of collagen complicates explanations of its behavior as a bioactive material, since conformational parameters for collagen molecules are deduced either from X- ray diffraction of fibers, or derived from properties of individual molecules in solution. Physiological interactions of collagen involve molecuies on the fiber surface. The anisotropic environment of these molecules can be expected to induce local conformational fluctuations relevant to intermolecular recognition and allosteric binding. We have examined conformational heterogeneity within the triple helix using stereochemical mapping, synthetic polypeptide models, and cryogenic atomic force microscopy. We have identified a 15-residue domain in alphal(l) chain residues 766 GTPGPQGIAGQRGVV 780' which shows equal preference for a strand-bendstrand conformation and for the collagen fold. A synthetic peptide analogous to this sequence generates a beta-rich structure in mixed solvents with the central -IA- residues forming the core of a betap-bend. This peptide is a potent force-conducting ligand for collagen receptors, serving as an anchorage for cells for tissue engineering. Our studies provide a rational mechanism for intermolecular recognition based on local conformational tautomerism of a helix-domain sequence.