Human red cell aquaporin CHIP. I. Molecular characterization of ABH and Colton blood group antigens.
Blood group antigens are structural variants in surface carbohydrate or amino acid polymorphisms on extracellular domains of membrane proteins. The red cell water channel-forming integral protein (Aquaporin CHIP) is a homotetramer with only one N-glycosylated subunit, however no CHIP-associated blood group antigens have yet been identified. Immunoblotting, monosaccharide composition analysis, and selective glycosidase digestions revealed that the CHIP-associated oligosaccharide contains ABH determinants and resembles a band 3-type glycan that cannot be cleaved from intact membranes by Peptide:N-glycosidase F. The molecular structure of the Colton antigens was previously unknown, but CHIP was selectively immunoprecipitated with anti-Coa or anti-Co(b). The DNA sequence from Colton-typed individuals predicted that residue 45 is alanine in the Co(a+b-) phenotype and valine in the Co(a-b+) phenotype. The nucleotide polymorphism corresponds to a PflMI endonuclease digestion site in the DNA from Co(a-b+) individuals. These studies have defined antigens within two blood group systems on CHIP: (a) an ABH-bearing polylactosaminoglycan attached to a poorly accessible site in the native membrane; and (b) the Colton antigen polymorphism which may permit the identification of rare individuals with defective water channel expression.
Smith
B L
BL
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185.
Preston
G M
GM
Spring
F A
FA
Anstee
D J
DJ
Agre
P
P
D000017:ABO Blood-Group System / Q000097:blood / Q000737:chemistry*; D051398:Aquaporin 1; D020346:Aquaporins; D001483:Base Sequence; D001789:Blood Group Antigens; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002460:Cell Line; D017931:DNA Primers; D004910:Erythrocyte Membrane / Q000737:chemistry*; D005091:Exons; D006801:Humans; D007473:Ion Channels / Q000097:blood* / Q000737:chemistry* / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000032:analysis; D009844:Oligosaccharides / Q000737:chemistry*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D015183:Restriction Mapping
D000017:ABO Blood-Group System; C496020:AQP1 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D017931:DNA Primers; D007473:Ion Channels; D046911:Macromolecular Substances; D009005:Monosaccharides; D009844:Oligosaccharides; D051398:Aquaporin 1