The pro-alpha3(V) collagen chain. Complete primary structure, expression domains in adult and developing tissues, and comparison to the structures and expression domains of the other types V and XI procollagen chains.
The low abundance fibrillar collagen type V is widely distributed in tissues as an alpha1(V)(2)alpha2(V) heterotrimer that helps regulate the diameters of fibrils of the abundant collagen type I. Mutations in the alpha1(V) and alpha2(V) chain genes have been identified in some cases of classical Ehlers-Danlos syndrome (EDS), in which aberrant collagen fibrils are associated with connective tissue fragility, particularly in skin and joints. Type V collagen also exists as an alpha1(V)alpha2(V)alpha3(V) heterotrimer that has remained poorly characterized chiefly due to inability to obtain the complete primary structure or nucleic acid probes for the alpha3(V) chain or its biosynthetic precursor, pro-alpha3(V). Here we provide human and mouse full-length pro-alpha3(V) sequences. Pro-alpha3(V) is shown to be closely related to the alpha1(V) precursor, pro-alpha1(V), but with marked differences in N-propeptide sequences, and collagenous domain features that provide insights into the low melting temperature of alpha1(V)alpha2(V)alpha3(V) heterotrimers, lack of heparin binding by alpha3(V) chains and the possibility that alpha1(V)alpha2(V)alpha3(V) heterotrimers are incorporated into heterotypic fibrils. In situ hybridization of mouse embryos detects alpha3(V) expression primarily in the epimysial sheaths of developing muscles and within nascent ligaments adjacent to forming bones and in joints. This distribution, and the association of alpha1(V), alpha2(V), and alpha3(V) chains in heterotrimers, suggests the human alpha3(V) gene COL5A3 as a candidate locus for at least some cases of classical EDS in which the alpha1(V) and alpha2(V) genes have been excluded, and for at least some cases of the hypermobility type of EDS, a condition marked by gross joint laxity and chronic musculoskeletal pain. COL5A3 is mapped to 19p13.2 near a polymorphic marker that should be useful in analyzing linkage with EDS and other disease phenotypes.
Imamura
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Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA.
Scott
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Greenspan
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003094:Collagen / Q000145:classification / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004535:Ehlers-Danlos Syndrome / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011347:Procollagen / Q000737:chemistry*; D011498:Protein Precursors / Q000145:classification / Q000235:genetics*; D021382:Protein Sorting Signals / Q000235:genetics; D012333:RNA, Messenger / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D011347:Procollagen; D011498:Protein Precursors; D021382:Protein Sorting Signals; D012333:RNA, Messenger; C406808:pro-alpha3(V) collagen; D003094:Collagen