Triple-helix folding and its role in collagen diseases

The folding of the collagen triple-helix is a slow process and provides an opportunity to look at multichain molecular assembly. Circular dichroism and NMR spectroscopy arc used to directly monitor the folding of collagen-like triplehelical peptides. Our kinetic measurements are used as a basis for proposing detailed mechanisms of folding and illustrate the sequence dependent nature of the folding process. Defective folding has been implicated in various collagen diseases where a single amino acid substitution occurs in the Gly position of the (Gly X-Y)n repeating collagen sequence. A et of peptide models was designed to investigate the effect of a Gly->Ser substitution found in a non-lethal form of brittle bone disease. With this model system, NMR is used to define the conformation, dynamics and folding of the triple-helix at the Gly substitution site and at other defined positions. The observed asymmetric disruption of the triple-helix provides the first molecular description at a collagen disease site.