Hydrophobic cluster analysis and modeling of the human Rh protein three-dimensional structures

Callebaut, Isabelle; Dulin, Fabienne; Bertrand, Olivier; Ripoche, Pierre; Mouro, I; Colin, Yves; Mornon, J.‐P.; Cartron, Jean‐Pierre

doi:10.1016/j.tracli.2006.02.001

Cited by 67 publications

(81 citation statements)

References 72 publications

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“…4). 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).…”

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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“…Negative sequence numbers are assigned to the processed leader peptides of EcAmtB and NeRh50, hence the mature proteins as expressed in E. coli start at residue ϩ1. Transmembrane helices M1-M11 as observed in the NeRh50 structure and M0 as predicted (23) are indicated with bars below the aligned sequences. Residues with large interface contacts (see SI Fig.…”

Section: Nerh50 Trimer Interface As a Model For Mammalian Rhesus Oligmentioning

confidence: 99%

“…Rh30 proteins appear to have evolved from Rh50 proteins early in fish speciation (20). Unlike for Rh50 proteins, there is no evidence, either from experimental data (21,22) or from structural models (23,24), that Rh30 proteins function as ammonium transporters, and they are currently thought to have a structural role in the erythrocyte membrane (25).…”

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confidence: 99%

“…Sequence alignments suggest that other Amt proteins also have 11 TMH, whereas studies on human Rh proteins suggest that they have 12 TMH, the extra helix being at the N terminus (1,27). Both Rh50 and Rh30 proteins have been modeled on Amt proteins, and these models challenge the view of the Rh complex as a tetramer and favor a trimeric model (23,24). They also predict that Rh proteins should lack the high-affinity ammonium binding site seen on the extracellular face of Amt proteins.…”

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confidence: 99%

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The 1.3-Å resolution structure of Nitrosomonas europaea Rh50 and mechanistic implications for NH ₃ transport by Rhesus family proteins

Lupo

Durand

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

118

161

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The Rhesus (Rh) proteins are a family of integral membrane proteins found throughout the animal kingdom that also occur in a number of lower eukaryotes. The significance of Rh proteins derives from their presence in the human red blood cell membrane, where they constitute the second most important group of antigens used in transfusion medicine after the ABO group. Rh proteins are related to the ammonium transport (Amt) protein family and there is considerable evidence that, like Amt proteins, they function as ammonia channels. We have now solved the structure of a rare bacterial homologue (from Nitrosomonas europaea) of human Rh50 proteins at a resolution of 1.3 Å. The protein is a trimer, and analysis of its subunit interface strongly argues that all Rh proteins are likely to be homotrimers and that the human erythrocyte proteins RhAG and RhCE/D are unlikely to form heterooligomers as previously proposed. When compared with structures of bacterial Amt proteins, NeRh50 shows several distinctive features of the substrate conduction pathway that support the concept that Rh proteins have much lower ammonium affinities than Amt proteins and might potentially function bidirectionally. ammonia channel ͉ ammonium transport ͉ Rhesus 50 protein ͉ x-ray structure

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“…[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. 29,30 Red cell turnover accounts for the highly regulated processing of approximately 10 12 effete red cells per day.…”

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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Hydrophobic cluster analysis and modeling of the human Rh protein three-dimensional structures

Cited by 67 publications

References 72 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 1.3-Å resolution structure of Nitrosomonas europaea Rh50 and mechanistic implications for NH ₃ transport by Rhesus family proteins

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

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Hydrophobic cluster analysis and modeling of the human Rh protein three-dimensional structures

Cited by 67 publications

References 72 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 1.3-Å resolution structure of Nitrosomonas europaea Rh50 and mechanistic implications for NH 3 transport by Rhesus family proteins

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

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The 1.3-Å resolution structure of Nitrosomonas europaea Rh50 and mechanistic implications for NH ₃ transport by Rhesus family proteins