Glycophorin A (GPA) and Band 3 (also known as Anion Exchanger 1) are the two most abundant integral proteins in the red blood cell (RBC) membrane [1]. GPA facilitates the expression of Band 3 in the cell membrane [2], and the two proteins are co-precipitated by an anti-Wr b antibody [3]. Wr b , which is antithetical to Wr a [4], is a high-frequency antigen, and antibodies against it can cause haemolytic transfusion reactions [5]. Although it has been observed that Glu658 of Band 3 is a required amino acid for the formation of the Wr b antigen [6], a number of proposals have been put forward for the GPA site of interaction.Bruce et al. [6] proposed that the interaction occurs between residues 80-89 (formerly 61-70) of GPA, with Arg80 (formerly Arg61) potentially forming a charge-pair with Glu658 of Band 3. However, Huang et al. [7] have suggested that Arg80 is not crucial for the formation of the antigen, and that Wr b is reliant on a longer sequence in GPA: Val70 to Ile95 (formerly 51-76). This sequence is encoded by part of exon 3 and extends to the beginning of the transmembrane domain encoded in exon 5.Early computational prediction of Gly74 to Phe87 (formerly 55-68), using a small GPA peptide, presented as an a-helical region [8]. Poole et al. [9] showed that the alteration of GPA Ala84 (formerly Ala65)?Pro resulted in formation of an aberrant Wr b . They concluded that because Proline is a helix breaker, this polymorphism disrupted the proposed a-helical structure. When modelling various small GPA peptides in our group, similar a-helices were seen. However, when modelling the complete extracellular domain of the GPA monomer (performed using de novo techniques facilitated by the Robetta software [10]), it appeared to be comprised of 3 to 5 bstrands. After 200-ns molecular dynamics simulations
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