Exon/intron structure of the human alpha 3(IV) gene encompassing the Goodpasture antigen (alpha 3(IV)NC1). Identification of a potentially antigenic region at the triple helix/NC1 domain junction.
The Goodpasture antigen has been identified as the non-collagenous (NC1) domain of alpha 3(IV), a novel collagen IV chain (Saus, J., Wieslander, J., Langeveld, J., Quinones, S., and Hudson, B.G. (1988) J. Biol. Chem. 263, 13374-13380). In the present study, the exon/intron structure and sequence for 285 amino acids of human alpha 3(IV), comprising 53 amino acids of the triple-helical domain and the complete NC1 domain (232 amino acids), were determined. Based on the comparison of the amino acid sequences of the alpha 1(IV), alpha 2(IV), alpha 3(IV), and alpha 5(IV) NC1 domains, a phylogenetic tree was constructed which indicates that alpha 2(IV) was the first chain to evolve, followed by alpha 3(IV), and then by alpha 1(IV) and alpha 5(IV). The exon/intron structure of these domains is consistent with this evolution model. In addition, it appears that alpha 3(IV) changed most after diverging from the parental gene. Analysis of its primary structure reveals that, at the junction between the triple-helical and NC1 domains, there exists a previously unrecognized, highly hydrophilic region (GLKGKRGDSGSPATWTTR) which is unique to the human alpha 3(IV) chain, containing a cell adhesion motif (RGD) as an integral part of a sequence (KRGDSGSP) conforming to a number of protein kinase recognition sites. Based on primary structure data, we outline new aspects to be explored concerning the molecular basis of collagen IV function and Goodpasture syndrome.
Quinones
S
S
Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway 08854.
Bernal
D
D
García-Sogo
M
M
Elena
S F
SF
Saus
J
J
D000595:Amino Acid Sequence; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics; D003094:Collagen / Q000235:genetics*; D024141:Collagen Type IV; D016384:Consensus Sequence; D004247:DNA; D004331:Drosophila melanogaster / Q000235:genetics; D005091:Exons; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain; D003094:Collagen; D004247:DNA; D011494:Protein Kinases