title: Glycine Substitutions in Collagen Heterotrimers Alter Triple Helical Assembly.
abstract: Osteogenesis imperfecta typically results from missense mutations in the collagen genome where the required glycine residues are replaced with another amino acid. Many models have attempted to replicate the structure of mutated collagen on the triple helix level. However, composition and register control of the triple helix is complicated and requires extreme precision, especially when these destabilizing mutations are present. Here we present mutations to a composition- and register-controlled AAB helix where one of the requisite glycines in the A chain of the triple helix is changed to serine or alanine. We see a loss of compositional control when the A chain is mutated, resulting in an A'BB composition that minimizes the number of mutations included in the triple helix. However, when both A and B chains are mutated and no nonmutated peptide chains are available, the designed A'A'B' composition is reestablished. Our work shows the ability of the mutations to influence and alter the composition and register of the collagen triple helix.
authors.affiliation: Department of Chemistry, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Clements
authors.affiliation: Department of Chemistry, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Acevedo-Jake
authors.affiliation: Department of Chemistry, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Walker
authors.affiliation: Department of Chemistry, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Jeffrey D
authors.identifier: 0000-0002-3186-5395
authors.initials: JD
authors.lastname: Hartgerink
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D024042:Collagen Type I / Q000737:chemistry* / Q000235:genetics; D005998:Glycine / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D056004:Molecular Dynamics Simulation; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D017385:Sequence Homology
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D005998:Glycine