Creative Biostructure has developed custom MemPro™ gene-to-structure services for membrane protein glycophorins. Membrane-spanning glycophorins are the major sialoglycoproteins of red blood cells (RBCs) and rich in sialic acid, which makes the membrane of RBC hydrophilic and enables RBCs to circulate without adhering.
Glycophorins include glycophorin A (GYPA), glycophorin B (GYPB), glycophorin C (GYPC), glycophorin D (GYPD) and glycophorin E (GYPE), listed in the order of their expression levels. GYPA is the predominant RBC glycophorin and GYPE is the least. GYPA, GYPB and GYPE are organized in the same chromosome and highly homologous. GYPA and GYPB bear antigen determinants of MNSs blood group system: GYPA is for M and N while GYPB for S and s. GYPE may also carry the M blood antigen group antigen. GPC and GPD are closely related but have no structural homology to GYPA and GYPB. GYPD is a variant of GYPC, and they play an important role in regulating the cell shape and mechanical stability of red cells.
Figure. Three dimensional model of glycophorins A (GYPA) and B (GYPB).
The RBC glycophorins including GPA, GPB, GPC, GPD and GPE have been fully understood at DNA and protein levels. GPA is a class I transmembrane protein. The gene of GPA is located on 4q28-q31 containing 7 exons enconding 131 amino acids. The first exon encodes a leader peptide. The second to fourth exons are responsible for the exoplasmic domain of GPA which has the codons for M and N blood group antigens, the exons 5 and 6 are for the membrane-spanning domain and cytoplasmic domain respectively. The secondary structure of GPA is 20% β sheet. GPA contributes to maintain the mature RBC membrane to be a net negative surface charge, preventing RBC aggregation. GPB is also a class I transmembrane protein containing 70 amino acids. The exons 1 trough 5 of GPB has similar sequence with that of GPA. The extracellular domain of GPB decides Ss-blood group type at amino acid residue 29 (shown in the figure). Methionine imparts S phenotype while threonine imparts s phenotype. GPE is a new member of GPA and GPB family. Unlike GPA and GPB, the gene encoding GPC and GPD is a single gene that is located on 2q14-q21. GPC contributes to maintain cell shape, regulate membrane mechanical stability and membrane deformability of mature RBCs.
Creative Biostructure can provide custom MemPro™ gene-to-structure services for membrane proteins. Please click for more information.
Joel Anne Chasis and Narla Mohandas. Red blood cell glycophorins. Blood. 1992 Oct 15;80(8):1869-79.