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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.

Original publication

DOI

10.1038/nsmb.2389

Type

Journal article

Journal

Nat Struct Mol Biol

Publication Date

10/2012

Volume

19

Pages

1031 - 1036

Keywords

Amino Acid Sequence, Collagen Diseases, Collagen Type III, Crystallography, X-Ray, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Mutation, Missense, Protein Multimerization, Protein Structure, Tertiary