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. 1990 Sep-Oct;63(5):461–467.

Biochemistry of the erythrocyte Rh polypeptides: a review.

P Agre 1, B L Smith 1, S Hartel-Schenk 1
PMCID: PMC2589356  PMID: 2127333

Abstract

The clinically important Rh blood group system is complex, consisting of multiple distinct antigens. Despite clinical recognition for over 50 years, the Rh blood group antigens have remained poorly understood on a molecular level until the recent identification and characterization of the "Rh polypeptides," the core structural proteins of the Rh antigens. This group of erythrocyte membrane proteins of molecular weight 30,000-35,000 daltons was first recognized by employing Rh-specific antibodies to immunoprecipitate radiolabeled components of erythrocyte membranes. By using antibodies specific for the Rh D, c, and E antigens, a series of highly related non-identical proteins were immunoprecipitated, indicating that the Rh antigens are composed of multiple related proteins. The Rh polypeptides have been purified and characterized, and they were found to have several unusual biochemical characteristics. The Rh polypeptides penetrate the membrane bilayer; they are linked to the underlying membrane skeleton; they are covalently fatty acid acylated with palmitate. While the Rh antigenic reactivity is unique to human erythrocytes, the Rh polypeptides have been isolated from erythrocytes of diverse species and are thought to be fundamental components of all mammalian erythrocyte membranes. The functional role of the Rh polypeptides remains undefined, but a role in the organization of membrane phospholipid is suspected.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agre P., Saboori A. M., Asimos A., Smith B. L. Purification and partial characterization of the Mr 30,000 integral membrane protein associated with the erythrocyte Rh(D) antigen. J Biol Chem. 1987 Dec 25;262(36):17497–17503. [PubMed] [Google Scholar]
  2. Avent N. D., Ridgwell K., Mawby W. J., Tanner M. J., Anstee D. J., Kumpel B. Protein-sequence studies on Rh-related polypeptides suggest the presence of at least two groups of proteins which associate in the human red-cell membrane. Biochem J. 1988 Dec 15;256(3):1043–1046. doi: 10.1042/bj2561043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Avent N., Judson P. A., Parsons S. F., Mallinson G., Anstee D. J., Tanner M. J., Evans P. R., Hodges E., Maciver A. G., Holmes C. Monoclonal antibodies that recognize different membrane proteins that are deficient in Rhnull human erythrocytes. One group of antibodies reacts with a variety of cells and tissues whereas the other group is erythroid-specific. Biochem J. 1988 Apr 15;251(2):499–505. doi: 10.1042/bj2510499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ballas S. K., Clark M. R., Mohandas N., Colfer H. F., Caswell M. S., Bergren M. O., Perkins H. A., Shohet S. B. Red cell membrane and cation deficiency in Rh null syndrome. Blood. 1984 May;63(5):1046–1055. [PubMed] [Google Scholar]
  5. Blanchard D., Bloy C., Hermand P., Cartron J. P., Saboori A. M., Smith B. L., Agre P. Two-dimensional iodopeptide mapping demonstrates that erythrocyte Rh D, c, and E polypeptides are structurally homologous but nonidentical. Blood. 1988 Oct;72(4):1424–1427. [PubMed] [Google Scholar]
  6. Bloy C., Blanchard D., Dahr W., Beyreuther K., Salmon C., Cartron J. P. Determination of the N-terminal sequence of human red cell Rh(D) polypeptide and demonstration that the Rh(D), (c), and (E) antigens are carried by distinct polypeptide chains. Blood. 1988 Aug;72(2):661–666. [PubMed] [Google Scholar]
  7. Bloy C., Blanchard D., Lambin P., Goossens D., Rouger P., Salmon C., Cartron J. P. Human monoclonal antibody against Rh(D) antigen: partial characterization of the Rh(D) polypeptide from human erythrocytes. Blood. 1987 May;69(5):1491–1497. [PubMed] [Google Scholar]
  8. Conboy J., Mohandas N., Tchernia G., Kan Y. W. Molecular basis of hereditary elliptocytosis due to protein 4.1 deficiency. N Engl J Med. 1986 Sep 11;315(11):680–685. doi: 10.1056/NEJM198609113151105. [DOI] [PubMed] [Google Scholar]
  9. Gahmberg C. G., Karhi K. K. Association of Rho(D) polypeptides with the membrane skeleton in Rho(D)-positive human red cells. J Immunol. 1984 Jul;133(1):334–337. [PubMed] [Google Scholar]
  10. Gahmberg C. G. Molecular characterization of the human red cell Rho(D) antigen. EMBO J. 1983;2(2):223–227. doi: 10.1002/j.1460-2075.1983.tb01409.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gahmberg C. G. Molecular identification of the human Rho (D) antigen. FEBS Lett. 1982 Apr 5;140(1):93–97. doi: 10.1016/0014-5793(82)80528-0. [DOI] [PubMed] [Google Scholar]
  12. Green F. A. Phospholipid requirement for Rh antigenic activity. J Biol Chem. 1968 Oct 25;243(20):5519–5521. [PubMed] [Google Scholar]
  13. Hughes-Jones N. C., Green E. J., Hunt V. A. Loss of rh antigen activity following the action of phospholipase A2 on red cell stroma. Vox Sang. 1975;29(3):184–191. doi: 10.1111/j.1423-0410.1975.tb00493.x. [DOI] [PubMed] [Google Scholar]
  14. Kuypers F., van Linde-Sibenius-Trip M., Roelofsen B., Tanner M. J., Anstee D. J., Op den Kamp J. A. Rhnull human erythrocytes have an abnormal membrane phospholipid organization. Biochem J. 1984 Aug 1;221(3):931–934. doi: 10.1042/bj2210931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lauf P. K., Joiner C. H. Increased potassium transport and ouabain binding in human Rhnull red blood cells. Blood. 1976 Sep;48(3):457–468. [PubMed] [Google Scholar]
  16. Masouredis S. P., Sudora E. J., Mahan L., Victoria E. J. Antigen site densities and ultrastructural distribution patterns of red cell Rh antigens. Transfusion. 1976 Mar-Apr;16(2):94–106. doi: 10.1046/j.1537-2995.1976.16276155121.x. [DOI] [PubMed] [Google Scholar]
  17. McGuire M., Smith B. L., Agre P. Distinct variants of erythrocyte protein 4.1 inherited in linkage with elliptocytosis and Rh type in three white families. Blood. 1988 Jul;72(1):287–293. [PubMed] [Google Scholar]
  18. Moore S., Green C. The identification of specific Rhesus-polypeptide-blood-group-ABH-active-glycoprotein complexes in the human red-cell membrane. Biochem J. 1987 Jun 15;244(3):735–741. doi: 10.1042/bj2440735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moore S., Woodrow C. F., McClelland D. B. Isolation of membrane components associated with human red cell antigens Rh(D), (c), (E) and Fy. Nature. 1982 Feb 11;295(5849):529–531. doi: 10.1038/295529a0. [DOI] [PubMed] [Google Scholar]
  20. Ridgwell K., Roberts S. J., Tanner M. J., Anstee D. J. Absence of two membrane proteins containing extracellular thiol groups in Rhnull human erythrocytes. Biochem J. 1983 Jul 1;213(1):267–269. doi: 10.1042/bj2130267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ridgwell K., Tanner M. J., Anstee D. J. The Rhesus (D) polypeptide is linked to the human erythrocyte cytoskeleton. FEBS Lett. 1984 Aug 20;174(1):7–10. doi: 10.1016/0014-5793(84)81066-2. [DOI] [PubMed] [Google Scholar]
  22. Saboori A. M., Denker B. M., Agre P. Isolation of proteins related to the Rh polypeptides from nonhuman erythrocytes. J Clin Invest. 1989 Jan;83(1):187–191. doi: 10.1172/JCI113857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Saboori A. M., Smith B. L., Agre P. Polymorphism in the Mr 32,000 Rh protein purified from Rh(D)-positive and -negative erythrocytes. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4042–4045. doi: 10.1073/pnas.85.11.4042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schroit A. J., Madsen J., Ruoho A. E. Radioiodinated, photoactivatable phosphatidylcholine and phosphatidylserine: transfer properties and differential photoreactive interaction with human erythrocyte membrane proteins. Biochemistry. 1987 Apr 7;26(7):1812–1819. doi: 10.1021/bi00381a004. [DOI] [PubMed] [Google Scholar]
  25. Seigneuret M., Devaux P. F. ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3751–3755. doi: 10.1073/pnas.81.12.3751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sturgeon P. Hematological observations on the anemia associated with blood type Rhnull. Blood. 1970 Sep;36(3):310–320. [PubMed] [Google Scholar]
  27. Suyama K., Goldstein J. Antibody produced against isolated Rh(D) polypeptide reacts with other Rh-related antigens. Blood. 1988 Nov;72(5):1622–1626. [PubMed] [Google Scholar]
  28. Suyama K., Goldstein J. Enzymatic evidence for differences in the placement of Rh antigens within the red cell membrane. Blood. 1990 Jan 1;75(1):255–260. [PubMed] [Google Scholar]
  29. Wiener A. S. THE Rh SERIES OF ALLELIC GENES. Science. 1944 Dec 29;100(2609):595–597. doi: 10.1126/science.100.2609.595. [DOI] [PubMed] [Google Scholar]
  30. de Vetten M. P., Agre P. The Rh polypeptide is a major fatty acid-acylated erythrocyte membrane protein. J Biol Chem. 1988 Dec 5;263(34):18193–18196. [PubMed] [Google Scholar]

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