Abstract
Type XIX collagen was discovered from the sequence of rhabdomyosarcoma cDNA clones. The chain is composed of a 268-residue amino terminus, an 832-residue discontinuous collagenous region, and a 19-residue carboxyl peptide. Light microscopy immunohistochemistry of adult human tissues demonstrated that type XIX is localized in vascular, neuronal, mesenchymal, and some epithelial basement membrane zones. It also appears to be involved in events linked to skeletal myogenesis. In this report, we have presented the first direct evidence for the molecular structure of type XIX collagen. Using human umbilical cord, native type XIX was purified by neutral salt extraction and by ion exchange and antibody affinity chromatography. Type XIX was found to represent only approximately 10(-6)% of the dry weight of tissue, making it by far the least abundant collagen ever isolated. Transmission electron microscopy after rotary shadowing revealed the appearance of rodlike structures with multiple sharp bends, a small nodule at one end of the molecule, and a total length of 240 nm. Domain-specific antibodies were used to identify the nodule as the noncollagenous amino terminus, whereas the location of most kinks corresponds to major interruptions separating the five collagenous subdomains. More than half of the type XIX molecules observed were present in oligomers of different size and complexity, resulting from association of the amino-terminal domains. Biochemical analysis demonstrated that these supramolecular aggregates are dependent upon and/or stabilized by intermolecular disulfide cross-links and that the globular amino terminus contains a high affinity, heparin-binding site. The polymorphic conformational states of this rare collagen, and its ability to self-assemble into a higher order structure provide focal points for future determination of biologically significant functions in cell-cell and/or cell-matrix interactions.
Highlights
Twenty-six collagen types have currently been designated; seven of these are recent discoveries, and several have yet to be described [1,2,3,4,5,6,7]
In the most general sense, collagens have been divided into the classic fibrillar group and the nonfibrillar group, a highly heterogeneous class exhibiting a spectrum of sizes, supramolecular assemblies, and chain organization, with the one commonality being the presence of noncollagenous sequences interrupting and/or flanking collagenous domains (1, 2, 8 –10)
Immunoblots of crude extract prepared from human placenta and umbilical cord were negative for type XIX, so conventional procedures were employed to enrich the preparation for matrix proteins [28]
Summary
Twenty-six collagen types have currently been designated; seven of these are recent discoveries, and several have yet to be described [1,2,3,4,5,6,7]. The type XIX chain is composed of a 268-residue, noncollagenous amino terminus, an 832-residue discontinuous collagenous region, and a 19-residue carboxyl peptide (14 –16). Several features in the type XIX sequence place this collagen in the largest subclass of the nonfibrillar group, together with types IX, XII, XIV, XVI, XX, and XXI [2,3,4, 10] These include an ϳ250-residue thrombospondin module in the amino terminus (Tsp-N), the position of two 2-amino acid interruptions in the collagenous subdomain closest to the carboxyl terminus, and a Cys-Xaa4-Cys motif situated at the junction of the collagenous region and carboxyl peptide [10, 15, 16]. The involved amino-terminal domain is responsible for intermolecular disulfide linkages and contains a proven heparin-binding site
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
