Type I collagen is an important protein in connective tissues such as bone. Collagen forms a trimer that is capable of self-association to form fibers. These fibers then become incorporated into bone during mineralization. Mutations in type I collagen lead to Osteogenesis Imperfecta (Ol) where there is defective bone formation. Mutations resulting in the substitution of one Gly residue within the repeating (Gly-Xaa- Yaa)n pattern of type I collagen triple helix are the major cause of Ol. Collagen folding in the presence of a mutation has been shown to be delayed. Our hypothesis is that this delay in folding is due to a pause at the mutation site leading to an intermediate state stable enough to have a significant impact on folding. Collagen model peptides will be used to study how type I collagen propagates through a glycine mutation in Ol using Circular Dichroism (CD) and Differential Scanning Calorimetry (DSC). This study aims to determine whether the effects of different Gly mutations on collagen folding can ultimately provide insight into the varying phenotypes observed in Ol patients.
| Bryan, Michael A; Cheng, Haiming; Brodsky, Barbara (2011) Sequence environment of mutation affects stability and folding in collagen model peptides of osteogenesis imperfecta. Biopolymers 96:4-13 |
| Hyde, Timothy J; Bryan, Michael A; Brodsky, Barbara et al. (2006) Sequence dependence of renucleation after a Gly mutation in model collagen peptides. J Biol Chem 281:36937-43 |
| Kar, Karunakar; Amin, Priyal; Bryan, Michael A et al. (2006) Self-association of collagen triple helic peptides into higher order structures. J Biol Chem 281:33283-90 |
