Primary structures of variant hybrid glycophorins

Abstract

Glycophorins {dollar}\alpha{dollar} and {dollar}\delta{dollar} are two major sialic acid-rich glycoproteins found in the membrane of human erythrocytes. They bear the antigenic epitopes that define MN and Ss blood groups, respectively. In this study, three variant glycophorins from erythrocytes of three individuals who exhibit unusual blood group phenotypes, MiV(J.L.), St{dollar}\sp{lcub}\rm a{rcub}{dollar}, and MiIII were isolated and their amino acid sequences were determined. All three were hybrid proteins composed solely of sequences originating from {dollar}\alpha{dollar} and {dollar}\delta{dollar} glycophorins.;MiV(J.L.) glycophorin was found to have an {dollar}\alpha{dollar}-{dollar}\delta{dollar} hybrid arrangement in which the amino-terminal sequence, residues 1-59, is identical to that of M-{dollar}\alpha{dollar} glycophorin and the carboxyl-terminal sequence of residues, 60-100, is identical to that of S-{dollar}\delta{dollar} glycophorin. St{dollar}\sp{lcub}\rm a{rcub}{dollar} glycophorin had a {dollar}\delta{dollar}-{dollar}\alpha{dollar} hybrid arrangement exactly reciprocal to that of MiV(J.L.) glycophorin in which the amino-terminal residues derive from the {dollar}\delta{dollar} glycophorin sequence while the carboxyl-terminal residues derive from the {dollar}\alpha{dollar} glycophorin sequence. MiIII glycophorin is a {dollar}\delta{dollar}-{dollar}\alpha{dollar}-{dollar}\delta{dollar} hybrid glycophorin. It is {dollar}\delta{dollar}-like but contains a stretch of 10 residues homologous to the {dollar}\alpha{dollar} sequence. It also contains a segment that derives from intron 2 of the {dollar}\delta{dollar} glycophorin gene.;Synthetic peptides corresponding to the hybrid {dollar}\alpha{dollar}-{dollar}\delta{dollar} junctions of MiV(J.L.) and MiIII glycophorins were prepared. The synthetic peptides specifically inhibited the hemagglutinations of MiV(J.L.) and MiIII erythrocytes by antisera used to define their variant phenotypes. This demonstrates that the sequences created at the hybrid junctions contain the antigenic epitopes that specify the variant phenotypes of the erythrocytes.;MiV(J.L.), St{dollar}\sp{lcub}\rm a{rcub}{dollar} and MiIII glycophorins, as well as possibly other variant glycophorins of Miltenberger phenotypes, may have arisen by a common genetic mechanism, namely, unequal homologous recombinations between misaligned {dollar}\alpha{dollar} and {dollar}\delta{dollar} glycophorin genes. The hybrid junctions of the resulting variant glycophorins specify the antigenic determinants that define the variant phenotypes of the erythrocytes.