Complete primary structure of the sixth chain of human basement membrane collagen, alpha 6(IV). Isolation of the cDNAs for alpha 6(IV) and comparison with five other type IV collagen chains.
Basement membranes were previously believed to contain five distinct type IV collagen subunits. We have recently isolated part of the cDNA for a novel type IV collagen, alpha 6(IV), and shown that COL4A6, the gene encoding this new chain, is deleted in Alport syndrome-associated leiomyomatosis (Zhou, J., Mochizuki, T., Smeets, H., Antignac, C., Laurila, P., de Paepe, A., Tryggvason, K., and Reeders, S. T. (1993) Science 261, 1167-1169). Here, we describe the entire human alpha 6(IV) cDNA and show that the gene encodes a classical type IV collagen with homology throughout its length to all the other five chains. There is a 21-residue signal peptide, a 1417-residue collagenous domain interrupted at 25 points, and a 228-residue carboxyl-terminal non-collagenous domain. When the complete primary structure of this new chain was compared with all the other known chains, it became clear that alpha 6(IV) has the most resemblance to alpha 2(IV) and alpha 4(IV). The evolution of the six chains was deduced, allowing a new classification of the type IV collagen family. The alpha 6(IV) chain is a candidate gene for X-linked Alport syndrome; knowledge of the complete structure of the chain will permit us to screen systematically for mutations in patients and to generate recombinant proteins and synthetic peptides for further study of cell-matrix interactions involving the alpha 6(IV) chain.
Zhou
J
J
Department of Nephrology, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Ding
M
M
Zhao
Z
Z
Reeders
S T
ST
D000595:Amino Acid Sequence; D001483:Base Sequence; D001485:Basement Membrane / Q000378:metabolism*; D005075:Biological Evolution; D015152:Blotting, Northern; D003094:Collagen / Q000235:genetics*; D018076:DNA, Complementary; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D003094:Collagen