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Nat Struct Mol Biol. 2012 Oct;19(10):1031-6. doi: 10.1038/nsmb.2389. Epub 2012 Sep 23.

Structural basis of fibrillar collagen trimerization and related genetic disorders.

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1
Formation de Recherche en Evolution 3310, Institut de Biologie et Chimie des Protéines, Centre National de la Recherche Scientifique, Université Lyon 1, Lyon, France.

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.

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PMID:
23001006
PMCID:
PMC3465578
DOI:
10.1038/nsmb.2389
[Indexed for MEDLINE]
Free PMC Article

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