Structural and functional features of the .alpha.3 chain indicate a bridging role for chicken collagen VI in connective tissues

Abstract

Type VI collagen is a component of 100 nm long periodic filaments with a widespread distribution around collagen fibers and on the surface of cells. It is an unusual collagen constituted by three distinct chains, one of which (alpha 3) is much larger than the others and is encoded by a 9-kb mRNA. The amino acid sequence of the alpha 3(VI) deduced from the present cDNA clones specifies for a multidomain protein of at least 2648 residues made of a short collagenous sequence (336 residues), flanked at the N-terminus by nine 200 residue long repeating motifs and at the C-terminus by two similar motifs that share extensive identities with the collagen-binding type A repeats of von Willebrand factor. Type VI collagen and alpha 3(VI) fusion proteins bound to insolubilized type I collagen in a specific, time-dependent, and saturable manner. The alpha 3(VI) chain has three Arg-Gly-Asp sequences in the collagenous domain, and cell attachment was stimulated by the triple helix of type VI collagen and by alpha 3(VI) fusion proteins containing Arg-Gly-Asp sequences. This function was specifically inhibited by the Arg-Gly-Asp-Ser synthetic peptide. The type I collagen-binding and the cell-attachment properties of the alpha 3(VI) chain provide direct information for the role of type VI collagen in connective tissues.

Cartilage matrix protein is a component of the collagen fibril of cartilage

“…The amino acid sequence of this molecule has been deduced from the corresponding cDNA (Argraves et al, 1987) and genomic DNA (Kiss et al, 1989), and shows a central region with considerable homology to an EGF-precursor motif. On either side of this EGF-like region is a 190-amino acid motif (the CMP-motif) with homology to regions of several proteins, including von Willebrand factor Shelton-Inloes et al, 1986;Titani et al, 1986), complement factors B (Mole et al, 1984) and C2 (Bentley, 19861, type VI collagen (Bonaldo and Colombatti, 1989;Koller et al, 1989;Bonaldo et al, 1990), and the alpha chains of the integrins Mac-1 (Pytela, 1988;Corbi et al, 19881, p150,95 (Corbi et al, 1987), LFA-1 (Corbi et al, 1987), and VLA-2 (Takada and Hemler, 1989).…”

Tenascin variants: differential binding to fibronectin and distinct distribution in cell cultures and tissues.

“…Often the biological significance is unknown, but in several cases the alternatively spliced regions were postulated to be important for the interaction with other extracellular matrix components as in elastin (Pollock et a., 1990), type IX collagen (Svoboda et a!., 1988), or type VI collagen (Chu et a., 1989(Chu et a., , 1990). In the case of type VI collagen, experimental evidence was presented for the interaction of its so-called A-domains with collagen type I (Bonaldo et al, 1990). Because some of these A-domains are subject to alternative splicing, it was postulated that the type VI collagen variants could differ by their affinity for type I collagen.…”

Type VI Collagen Anchors Endothelial Basement Membranes by Interacting with Type IV Collagen

“…They are present in all connective tissues that contain type I and type III collagen fibers and in cartilage, a tissue that contains predominantly type II collagen. The major functions that have been suggested for type VI collagen filamentous networks are as a substrate for cell attachment and as an anchoring meshwork that connects collagen fibers, nerves, and blood vessels to the surrounding matrix (1,2). This implies that not only is there an interaction, either direct or indirect, with the type I/III collagen fibers but also that there is an interaction with components of endothelial basement membranes.…”

“…One group reported no binding to types I, III, and IV collagens or fibronectin (9), while the second reported specific binding to fibrillar type I collagen (2). Other experiments using pepsin-solubilized type VI collagen, which only contains a small remnant of the globular domains, showed binding to fibronectin (8), while others found no binding to fibronectin or type I and III collagens but found binding to type II (4) and XIV collagens (10).…”