title: Structural heterogeneity of type I collagen triple helix and its role in osteogenesis imperfecta.
abstract: We investigated regions of different helical stability within human type I collagen and discussed their role in intermolecular interactions and osteogenesis imperfecta (OI). By differential scanning calorimetry and circular dichroism, we measured and mapped changes in the collagen melting temperature (DeltaTm) for 41 different Gly substitutions from 47 OI patients. In contrast to peptides, we found no correlations of DeltaTm with the identity of the substituting residue. Instead, we observed regular variations in DeltaTm with the substitution location in different triple helix regions. To relate the DeltaTm map to peptide-based stability predictions, we extracted the activation energy of local helix unfolding (DeltaG) from the reported peptide data. We constructed the DeltaG map and tested it by measuring the H-D exchange rate for glycine NH residues involved in interchain hydrogen bonds. Based on the DeltaTm and DeltaG maps, we delineated regional variations in the collagen triple helix stability. Two large, flexible regions deduced from the DeltaTm map aligned with the regions important for collagen fibril assembly and ligand binding. One of these regions also aligned with a lethal region for Gly substitutions in the alpha1(I) chain.
authors: Section on Physical Biochemistry, Bone and Extracellular Matrix Branch, NICHD, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Elena
authors: E
authors: Makareeva
authors: Edward L
authors: EL
authors: Mertz
authors: Natalia V
authors: NV
authors: Kuznetsova
authors: Mary B
authors: MB
authors: Sutter
authors: Angela M
authors: AM
authors: DeRidder
authors: Wayne A
authors: WA
authors: Cabral
authors: Aileen M
authors: AM
authors: Barnes
authors: Daniel J
authors: DJ
authors: McBride
authors: Joan C
authors: JC
authors: Marini
authors: Sergey
authors: S
authors: Leikin
mesh_terms: D002942:Circular Dichroism; D024042:Collagen Type I / Q000737:chemistry*; D006801:Humans; D010013:Osteogenesis Imperfecta; D010449:Peptide Mapping; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: D024042:Collagen Type I