Changes in the blood group Wright antigens are associated with a mutation at amino acid 658 in human erythrocyte band 3: a site of interaction between band 3 and glycophorin A under certain conditions [see comments]

Abstract

The Wright (Wr) blood group antigens, Wra and Wrb, have been suggested to be determined by alleles of the same gene. The Wrb antigen appears to involve both red blood cell (RBC) band 3 and glycophorin A (GPA). We have examined the cDNA sequences of the band 3 and GPA of one of the two known Wr(a+b-) individuals. We show that this individual is homozygous for the mutation Glu658--<Lys in band 3, but has normal GPA. Putative heterozygotes with Wr(a+b+) RBCs have both Glu and Lys at residue 658 of band 3, whereas the common Wr(a-b+) RBC phenotype only have band 3 with Glu658. The Wra and Wrb antigens are determined by the amino acid at residue 658 of band 3 and are antithetical. Examination of the amino acid sequence and Wrb antigen expression of GPA-related hybrid glycophorins suggests that Arg61 of GPA interacts with Glu658 of band 3 to form the Wrb antigen. We suggest that the interaction is stabilized by the presence of anti-Wrb antibodies and that this site of association between GPA and band 3 may be responsible for the previously reported ability of anti-GPA antibodies to decrease the deformability of RBCs.

Miltenberger blood group antigen subtype III (Mi.III) supports Wrb expression

“…In this study, we compared the expression of the Wright antigens in Mi.III vs. the non-Mi.III RBCs. The Wr a ⁄ Wr b dimorphism is determined by residue 658 of band 3: Lys-658 yields the Wright a (Wr a ) phenotype, whereas Glu-658 yields Wright b (Wr b ) [16]. Wr b is the predominant phenotype worldwide and in Taiwan.…”

Novel single‐nucleotide change in GYP*A in a person who made an alloantibody to a new high‐prevalence MNS antigen called ENEV

“…The altered expression of Wr b on the proband's RBCs is not unexpected because although the Wr b antigen is associated with glutamic acid at Amino Acid 658 of Band 3, its expression requires the presence of Amino Acid Residues 59 to 76 of GPA. 6,7 The amino acid changes associated with ENEP-and ENAV-phenotype RBCs are within this region of GPA and the RBCs have an altered expression of Wr b antigen. 8 Similarly, we have shown that the amino acid change at Residue 62 of GPA on ENEV-RBCs alters expression of Wr b .…”

Blood group antigens defined by the amino acid sequences of red cell surface proteins

“…It is becoming increasingly clear that different red cell surface proteins may associate together in the normal membrane. There is strong evidence that the two most abundant proteins, band 3 and GPA, are closely associated (Tanner, 1993a,b) and that the Wrb antigen may depend upon this association (Bruce et al, 1994b). The Rh polypeptides associate with the Rh glycoprotein ( Fig.…”

“…In this case, amino acid 658 on the fourth extracellular loop is involved. In Wr"-negative cells residue 658 is glutamic acid whereas in Wrapositive cells it is lysine (Table 2, Bruce et al, 1994b).…”