Sequence analysis of alpha 1(VI) and alpha 2(VI) chains of human type VI collagen reveals internal triplication of globular domains similar to the A domains of von Willebrand factor and two alpha 2(VI) chain variants that differ in the carboxy terminus.
Amino acid sequences of human collagen alpha 1(VI) and alpha 2(VI) chains were completed by cDNA sequencing and Edman degradation demonstrating that the mature polypeptides contain 1009 and 998 amino acid residues respectively. In addition, they contain small signal peptide sequences. Both chains show 31% identity in the N-terminal (approximately 235 residues) and C-terminal (approximately 430 residues) globular domains which are connected by a triple helical segment (335-336 residues). Internal alignment of the globular sequences indicates a repetitive 200-residue structure (15-23% identity) occurring three times (N1, C1, C2) in each chain. These repeating subdomains are connected to each other and to the triple helix by short (15-30 residues) cysteine-rich segments. The globular domains possess several N-glycosylation sites but no cell-binding RGD sequences, which are exclusively found in the triple helical segment. Sequencing of alpha 2(VI) cDNA clones revealed two variant chains with a distinct C2 subdomain and 3' non-coding region. The repetitive segments C1, C2 and, to a lesser extent, N1 show significant identity (15-18%) to the collagen-binding A domains of von Willebrand factor (vWF) and they are also similar to some integrin receptors, complement components and a cartilage matrix protein. Since the globular domains of collagen VI come into close contact with triple helical segments during the formation of tissue microfibrils it suggests that the globular domains bind to collagenous structures in a manner similar to the binding of vWF to collagen I.
Chu
M L
ML
Department of Biochemistry, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107.
Pan
T C
TC
Conway
D
D
Kuo
H J
HJ
Glanville
R W
RW
Timpl
R
R
Mann
K
K
Deutzmann
R
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D046911:Macromolecular Substances; D003012:Microbial Collagenase; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D014841:von Willebrand Factor / Q000235:genetics*
D046911:Macromolecular Substances; D014841:von Willebrand Factor; D003094:Collagen; D004247:DNA; D003012:Microbial Collagenase