title: Structural basis of fibrillar collagen trimerization and related genetic disorders.
abstract: The C propeptides of fibrillar procollagens have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. Mutations in C propeptides are associated with several, often lethal, genetic disorders affecting bone, cartilage, blood vessels and skin. Here we report the crystal structure of a C-propeptide domain from human procollagen III. It reveals an exquisite structural mechanism of chain recognition during intracellular trimerization of the procollagen molecule. It also gives insights into why some types of collagen consist of three identical polypeptide chains, whereas others do not. Finally, the data show striking correlations between the sites of numerous disease-related mutations in different C-propeptide domains and the degree of phenotype severity. The results have broad implications for understanding genetic disorders of connective tissues and designing new therapeutic strategies.
authors.affiliation: Formation de Recherche en Evolution 3310, Institut de Biologie et Chimie des Protéines, Centre National de la Recherche Scientifique, Université Lyon 1, Lyon, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bourhis
authors.forename: Natacha
authors.initials: N
authors.lastname: Mariano
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Karl
authors.initials: K
authors.lastname: Harlos
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Exposito
authors.forename: E Yvonne
authors.initials: EY
authors.lastname: Jones
authors.forename: Catherine
authors.initials: C
authors.lastname: Moali
authors.forename: Nushin
authors.initials: N
authors.lastname: Aghajari
authors.forename: David J S
authors.initials: DJ
authors.lastname: Hulmes
mesh_terms: D000595:Amino Acid Sequence; D003095:Collagen Diseases / Q000235:genetics*; D024061:Collagen Type III / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D024061:Collagen Type III