Modelling the human rhesus proteins: implications for structure and function

Conroy, Matthew J.; Bullough, Per A.; Merrick, Mike; Avent, Neil D.

doi:10.1111/j.1365-2141.2005.05786.x

Cited by 96 publications

(124 citation statements)

References 57 publications

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“…Modeling of the human Rh50A protein based on the X-ray crystal structure of the E. coli AmtB protein has shown that Rh50A is likely to adopt a structure similar to that of AmtB, and Rh50A is expected to have a channel architecture very similar to that of AmtB (11,15). Indeed, we recently solved the X-ray crystal structure of Rh50 Ne (47a) and showed it to be a trimeric protein with a channel architecture very similar to that predicted by our previous homology modeling of Rh50A (15). Hence, Rh proteins appear to have many of the essential characteristics to facilitate ammonium uptake, and our empirical data with Rh50 Ne (Fig.…”

Section: Discussionmentioning

confidence: 99%

Evolution and Functional Characterization of the RH50 Gene from the Ammonia-Oxidizing Bacterium Nitrosomonas europaea

et al. 2007

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The family of ammonia and ammonium channel proteins comprises the Amt proteins, which are present in all three domains of life with the notable exception of vertebrates, and the homologous Rh proteins (Rh50 and Rh30) that have been described thus far only in eukaryotes. The existence of an RH50 gene in bacteria was first revealed by the genome sequencing of the ammonia-oxidizing bacterium Nitrosomonas europaea. Here we have used a phylogenetic approach to study the evolution of the N. europaea RH50 gene, and we show that this gene, probably as a component of an integron cassette, has been transferred to the N. europaea genome by horizontal gene transfer. In addition, by functionally characterizing the Rh50 Ne protein and the corresponding knockout mutant, we determined that NeRh50 can mediate ammonium uptake. The RH50 Ne gene may thus have replaced functionally the AMT gene, which is missing in the genome of N. europaea and may be regarded as a case of nonorthologous gene displacement.Since the first description of rhesus (Rh) antigens in 1940 by Landsteiner and Wiener (45), the Rh blood group has become, after the ABO group, the most clinically significant in transfusion medicine. It is the most polymorphic of human blood groups, consisting of at least 45 independent antigens, and is consequently also widely used in human population genetics studies. In humans, Rh antigens are carried by two erythrocyte membrane proteins, named RhD and RhCE, and are also referred to as Rh30 because of their apparent molecular mass of 30 to 32 kDa. These proteins are coded by two very similar paralogous genes (ca. 96% identical at the nucleotide level), located in tandem on chromosome 1p34-36. The human genome also codes for three other members of the Rh family, the Rh50 transmembrane glycoproteins (Rh50A/RhAG, Rh50B/ RhBG, and Rh50C/RhCG) that have an apparent molecular mass of 50 to 58 kDa (6). The Rh50A protein is erythroid specific, like Rh30, and is associated with Rh30 in a multiprotein complex in the red blood cell membrane (10). Rh50A expression is required for Rh blood group antigen expression at the red blood cell membrane (14), and its lack of expression results in the Rh-null phenotype (68). In mammals, the nonerythroid Rh50B and Rh50C proteins are expressed in the kidney, liver, and gastrointestinal tract (79).The clinical importance of the Rh30 proteins has tended to overshadow the status of the Rh50 proteins. However, RH50 genes have a much longer evolutionary history than RH30 and the latter are likely to have derived by duplication from an RH50-like ancestor (38, 52). Indeed, while RH50 genes are present in the genome of the basal deuterostome animals sequenced thus far, the sea urchin Strongylocentrotus purpuratus (echinoderms), Ciona intestinalis and Ciona savignyi (tunicates), and amphioxus (cephalochordates), RH30 genes are absent in these species. Moreover, RH50 and RH30 genes are both present in teleost fish, amphibians, and mammals. Molecular evolutionary analyses have shown that in mammals Rh50 proteins ...

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Section: Discussionmentioning

confidence: 99%

Evolution and Functional Characterization of the RH50 Gene from the Ammonia-Oxidizing Bacterium Nitrosomonas europaea

et al. 2007

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“…[5][6][7] The erythrocyte Rh blood group proteins are well known because of their importance in blood transfusion, but recent functional studies and structural modeling reveal that the Rh blood group proteins are members of an ancient family of proteins involved in ammonia transport. [8][9][10][11] Non-erythroid Rh proteins have now been found in other tissues including the kidney, liver, brain, and skin 12-15 , in locations where ammonia production and elimination occurs. The family of Rh proteins has now been expanded significantly through comparative genomics and structure-function studies that reveal the presence of Rh homologs in all domains of life.…”

Section: Introductionmentioning

confidence: 99%

The Structure and Function of the Rh Antigen Complex

Westhoff

2007

Seminars in Hematology

144

106

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The Rh system is one of the most important and complex blood group systems because of the large number of antigens and the serious complications for the fetus of a woman sensitized by transfusion or pregnancy. Major advances in our understanding of the Rh system have occurred with the cloning of the genes and with functional evidence that the Rh blood group proteins belong to an ancient family of membrane proteins involved in ammonia transport.The arrangement and configuration of the genes at the RH locus promotes genetic exchange, generating new antigens. Importantly, RH genetic testing can now be applied to clinical transfusion medicine and prenatal practice. This includes testing for RHD zygosity, confirmation or resolution of D antigen status, and detection of altered RHD and RHCE genes in individuals at risk for producing antibodies to high incidence Rh antigens, particularly sickle cell disease patients. The Rh proteins form a core complex that is critical to the structure of the erythrocyte membrane, and may play a physiologically role in the sequestration of blood ammonia. The Rh family of proteins now includes non-erythroid Rh homologs present in many other tissues, and comparative genomics reveals Rh homologs in all domains of life.

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“…The Rh proteins are glycosylated, comprising a group of Rh-50 proteins (having a molecular weight of ∼50 kDa). The crystallographic structure of the trimeric mammalian RhCG predicts the transport of NH 3 over NH 4 + (Gruswitz et al, 2010), presumably owing to the presence of two highly conserved histidine residues that were shown to be important for function similar to that of bacterial AmtB (see below; Conroy et al, 2005). Furthermore, Rh proteins are proposed to be CO 2 gas channels in addition to transporting ammonia Lupo et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Aedes aegypti Rhesus glycoproteins contribute to ammonia excretion by larval anal papillae

Durant

Chasiotis

Misyura

et al. 2016

Journal of Experimental Biology

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In larval Aedes aegypti, transcripts of the Rhesus-like glycoproteins AeRh50-1 and AeRh50-2 have been detected in the anal papillae, sites of ammonia (NH 3 /NH 4 + ) excretion; however, these putative ammonia transporters have not been previously localized or functionally characterized. In this study, we show that the AeRh50s co-immunolocalize with apical V-type H + -ATPase as well as with basal Na + /K + -ATPase in the epithelium of anal papillae. The doublestranded RNA-mediated knockdown of AeRh50-1 and AeRh50-2 resulted in a significant reduction in AeRh50 protein abundance in the anal papillae, and this was coupled to decreased ammonia excretion. The knockdown of AeRh50-1 resulted in decreased hemolymph [NH 4 + ] and pH whereas knockdown of AeRh50-2 had no effect on these parameters. We conclude that the AeRh50s are important contributors to ammonia excretion at the anal papillae of larval A. aegypti, which may be the basis for their ability to inhabit areas with high ammonia levels.

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Modelling the human rhesus proteins: implications for structure and function

Cited by 96 publications

References 57 publications

Evolution and Functional Characterization of the RH50 Gene from the Ammonia-Oxidizing Bacterium Nitrosomonas europaea

Evolution and Functional Characterization of the RH50 Gene from the Ammonia-Oxidizing Bacterium Nitrosomonas europaea

The Structure and Function of the Rh Antigen Complex

Aedes aegypti Rhesus glycoproteins contribute to ammonia excretion by larval anal papillae

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