Structure, function and significance of Rh proteins in red cells

Burton, Nick; Anstee, David J.

doi:10.1097/moh.0b013e328311f422

Cited by 34 publications

(30 citation statements)

References 39 publications

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“…For Rh glycoprotein homologs TMH1, 3, 5, 6, 8, and 10 are conserved with key amino acids, e.g., twin-His and twin-Phe. TMH0 is peripheral [78] as suggested [79,80], but TMH1:6, 2:7, 3:8, 4:9, and 5:10 each form a pair of TM domains packed close in the membrane [76][77][78]. The surface-charge across the lipid bilayer is asymmetric because ECL and ICL are coated by net negative and net positive charges, respectively (Fig.…”

Section: Fold Of Transmembrane Helicesmentioning

confidence: 99%

The Rh protein family: gene evolution, membrane biology, and disease association

Huang

2009

Cell. Mol. Life Sci.

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The Rh (Rhesus) genes encode a family of conserved proteins that share a structural fold of 12 transmembrane helices with members of the major facilitator superfamily. Interest in this family has arisen from the discovery of Rh factor's involvement in hemolytic disease in the fetus and newborn, and of its homologs widely expressed in epithelial tissues. The Rh factor and Rh-associated glycoprotein (RhAG), with epithelial cousins RhBG and RhCG, form four subgroups conferring upon vertebrates a genealogical commonality. The past decade has heralded significant advances in understanding the phylogenetics, allelic diversity, crystal structure, and biological function of Rh proteins. This review describes recent progress on this family and the molecular insights gleaned from its gene evolution, membrane biology, and disease association. The focus is on its long evolutionary history and surprising structural conservation from prokaryotes to humans, pointing to the importance of its functional role, related to but distinct from ammonium transport proteins.

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Section: Fold Of Transmembrane Helicesmentioning

confidence: 99%

The Rh protein family: gene evolution, membrane biology, and disease association

Huang

2009

Cell. Mol. Life Sci.

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“…As mentioned above, CD47 forms part of the Rh-band 3 supercomplex of the human erythrocyte membrane which may function to regulate CO2 and bicarbonate transport. [24][25][26] CD47 is substantially diminished in p4.2-deficient erythrocytes, which are also deficient in major components of the Rh complex, thus it is likely that CD47 interacts directly with protein 4.2 in human erythrocyte membranes, which does not appear to be the case in mice. 15,17 The Rh-band 3 complex includes the RhAG2-Rh protein trimer, 27,28 CD47, ICAM-4 and band 3 dimers/tetramers.…”

Section: Introductionmentioning

confidence: 99%

4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins

Jeremy¹,

Plummer²,

Head³

et al. 2009

Haematologica

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BackgroundProtein 4.1R is an important component of the red cell membrane skeleton. It imparts structural integrity and has transmembrane signaling roles by direct interactions with transmembrane proteins and other membrane skeletal components, notably p55 and calmodulin. Design and MethodsSpontaneous and ligation-induced phosphatidylserine exposure on erythrocytes from two patients with 4.1R deficiency were studied, using CD47 glycoprotein and glycophorin C as ligands. We also looked for protein abnormalities in the 4.1R -based multiprotein complex. ResultsPhosphatidylserine exposure was significantly increased in 4.1R-deficient erythrocytes obtained from the two different individuals when ligands to CD47 glycoprotein were bound. Spontaneous phosphatidylserine exposure was normal. 4.1R, glycophorin C and p55 were missing or sharply reduced. Furthermore there was an alteration or deficiency of CD47 glycoprotein and a lack of CD44 glycoprotein. Based on a recent study in 4.1R-deficient mice, we found that there are clear functional differences between interactions of human red cell 4.1R and its murine counterpart. ConclusionsGlycophorin C is known to bind 4.1R, and we have defined previously that it also binds CD47. From our evidence, we suggest that 4.1R plays a role in the phosphatidylserine exposure signaling pathway that is of fundamental importance in red cell turnover. The linkage of CD44 to 4.1R may be relevant to this process. CD44 and CD47 glycoproteins. Haematologica 2009;94:1354-1361. doi:10.3324/haematol.2009 This is an open-access paper. 4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins

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“…These observations suggest there is considerable functional redundancy, with D and CE proteins effectively substituting for each other (Figure 3). 62 A counterargument to the population mixing hypothesis would be provided by a clear demonstration of selection for DϪ phenotype by environmental factors. In a thorough review of early studies seeking to identify associations between the D polymorphism and diseases, Mourant et al 2 64 and therefore the mechanism of such an association is not clear.…”

Section: Org Frommentioning

confidence: 99%

The relationship between blood groups and disease

Anstee

2010

Blood

381

349

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The relative contribution of founder effects and natural selection to the observed distribution of human blood groups has been debated since blood group frequencies were shown to differ between populations almost a century ago. Advances in our understanding of the migration patterns of early humans from Africa to populate the rest of the world obtained through the use of Y chromosome and mtDNA markers do much to inform this debate. There are clear examples of protection against infectious diseases from inheritance of polymorphisms in genes encoding and regulating the expression of ABH and Lewis antigens in bodily secretions particularly in respect of Helicobacter pylori, norovirus, and cholera infections. However, available evidence suggests surviving malaria is the most significant selective force affecting the expression of blood groups. IntroductionHirszfeld and Hirszfeld 1 showed the frequencies of blood groups A and B differ between populations. Their observations raised fundamental questions regarding the causes of these differences, which were eloquently summarized by Mourant et al 2(p1) :Were the differences the result of random genetic drift and founder effects, in small populations which later multiplied and stabilized the original, fortuitous, frequencies, or were they the result of natural selection, arising from differences in fitness between the various blood groups, fitnesses which themselves depended upon locally determined features of the external environment?Mourant et al concluded that "most workers now agree that both processes are operative, but their relative importance remains in question." 2 We now have detailed information concerning almost all the genes giving rise to blood group polymorphisms, the structure of the gene products and the antigens themselves, and in many cases functional information sufficient to delineate mechanisms of interaction with external agents. [3][4][5] In addition, studies on the tracking of Y chromosome and mtDNA haplotypes in human populations provide us with unprecedented information concerning the significance of genetic drift and founder effects in determining the genetic background of different world populations. 6 Given this new information, it seems an appropriate time to revisit these questions and ask whether we are any nearer understanding the relative importance of natural selection and founder effects in determining the distribution of human blood groups. Infectious diseases and selection for ABO blood group antigensThe molecular basis of the ABO blood group system was elucidated in 1990. 7 The gene encodes a glycosyltransferase, which transfers N-acetyl D-galactosamine (group A) or D-galactose (group B) to the nonreducing ends of glycans on glycoproteins and glycolipids. The group O phenotype results from inactivation of the A1 glycosyltransferase gene, and the nonreducing ends of the corresponding glycans in group O subjects express the blood group H antigen ( Figure 1A). The ABH antigens are not confined to red cells but are widely expressed i...

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Structure, function and significance of Rh proteins in red cells

Cited by 34 publications

References 39 publications

The Rh protein family: gene evolution, membrane biology, and disease association

The Rh protein family: gene evolution, membrane biology, and disease association

4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins

The relationship between blood groups and disease

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