Nuclear magnetic resonance characterization of peptide models of collagen-folding diseases

Misfolding of the triple helix has been shown to play a critical role in co llagen diseases. The substitution of a single Gly by another amino acid bre aks the characteristic repeating (Gly-X-Y)(n) sequence pattern and results in connective tissue disease such as osteogenesis imperfecta. Nuclear magne tic resonance (NMR) studies of normal and mutated collagen triple-helical p eptides offer an opportunity to characterize folding and conformational alt erations at the substitution site, as well as at positions upstream and dow nstream of a Gly mutation. The NMR studies suggest that the local sequences surrounding the substitution site, and the renucleation sequences N-termin al to and adjacent to the substitution site, may be critical in defining th e clinical phenotype of osteogenesis imperfecta. These studies may pave the way to understanding the mechanism by which a single Gly substitution in c ollagen can lead to pathological conditions.