| Structural highlights
Disease
RHAG_HUMAN Rh deficiency syndrome;Overhydrated hereditary stomatocytosis. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
Function
RHAG_HUMAN Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Heterotrimer with RHCE (RHAG)2(RHCE), that transports ammonium and its related derivative methylammonium, in both neutral and ionic forms, across the erythrocyte membrane (PubMed:11062476, PubMed:11861637, PubMed:15572441, PubMed:15856280, PubMed:19273840, PubMed:21849667, PubMed:22012326, PubMed:24077989, PubMed:26354748). The transport of NH4(+) is electrogenic and masks the NH3 transport (PubMed:26354748). Also, may act as a CO2 channel (PubMed:17712059, PubMed:19273840, PubMed:24077989). In vitro, leaks monovalent cations (PubMed:18931342, PubMed:21849667). Moreover in erythrocyte, regulates RHD membrane expression (PubMed:12130520) and is associated with rhesus blood group antigen expression (PubMed:12130520, PubMed:19744193).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Publication Abstract from PubMed
The stability and shape of the erythrocyte membrane is provided by the ankyrin-1 complex, but how it tethers the spectrin-actin cytoskeleton to the lipid bilayer and the nature of its association with the band 3 anion exchanger and the Rhesus glycoproteins remains unknown. Here we present structures of ankyrin-1 complexes purified from human erythrocytes. We reveal the architecture of a core complex of ankyrin-1, the Rhesus proteins RhAG and RhCE, the band 3 anion exchanger, protein 4.2, glycophorin A and glycophorin B. The distinct T-shaped conformation of membrane-bound ankyrin-1 facilitates recognition of RhCE and, unexpectedly, the water channel aquaporin-1. Together, our results uncover the molecular details of ankyrin-1 association with the erythrocyte membrane, and illustrate the mechanism of ankyrin-mediated membrane protein clustering.
Architecture of the human erythrocyte ankyrin-1 complex.,Vallese F, Kim K, Yen LY, Johnston JD, Noble AJ, Cali T, Clarke OB Nat Struct Mol Biol. 2022 Jul;29(7):706-718. doi: 10.1038/s41594-022-00792-w. , Epub 2022 Jul 14. PMID:35835865[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Marini AM, Matassi G, Raynal V, Andre B, Cartron JP, Cherif-Zahar B. The human Rhesus-associated RhAG protein and a kidney homologue promote ammonium transport in yeast. Nat Genet. 2000 Nov;26(3):341-4. PMID:11062476 doi:https://dx.doi.org/10.1038/81656
- ↑ Westhoff CM, Ferreri-Jacobia M, Mak DO, Foskett JK. Identification of the erythrocyte Rh blood group glycoprotein as a mammalian ammonium transporter. J Biol Chem. 2002 Apr 12;277(15):12499-502. PMID:11861637 doi:10.1074/jbc.C200060200
- ↑ Mouro-Chanteloup I, D'Ambrosio AM, Gane P, Le Van Kim C, Raynal V, Dhermy D, Cartron JP, Colin Y. Cell-surface expression of RhD blood group polypeptide is posttranscriptionally regulated by the RhAG glycoprotein. Blood. 2002 Aug 1;100(3):1038-47 PMID:12130520
- ↑ Ripoche P, Bertrand O, Gane P, Birkenmeier C, Colin Y, Cartron JP. Human Rhesus-associated glycoprotein mediates facilitated transport of NH(3) into red blood cells. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17222-7. PMID:15572441 doi:10.1073/pnas.0403704101
- ↑ Benjelloun F, Bakouh N, Fritsch J, Hulin P, Lipecka J, Edelman A, Planelles G, Thomas SR, Chérif-Zahar B. Expression of the human erythroid Rh glycoprotein (RhAG) enhances both NH3 and NH4+ transport in HeLa cells. Pflugers Arch. 2005 Jun;450(3):155-67. PMID:15856280 doi:10.1007/s00424-005-1381-y
- ↑ Endeward V, Cartron JP, Ripoche P, Gros G. RhAG protein of the Rhesus complex is a CO2 channel in the human red cell membrane. FASEB J. 2008 Jan;22(1):64-73. PMID:17712059 doi:10.1096/fj.07-9097com
- ↑ Bruce LJ, Guizouarn H, Burton NM, Gabillat N, Poole J, Flatt JF, Brady RL, Borgese F, Delaunay J, Stewart GW. The monovalent cation leak in overhydrated stomatocytic red blood cells results from amino acid substitutions in the Rh-associated glycoprotein. Blood. 2009 Feb 5;113(6):1350-7. PMID:18931342 doi:10.1182/blood-2008-07-171140
- ↑ Musa-Aziz R, Chen LM, Pelletier MF, Boron WF. Relative CO2/NH3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG. Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5406-11. PMID:19273840 doi:10.1073/pnas.0813231106
- ↑ Tilley L, Green C, Poole J, Gaskell A, Ridgwell K, Burton NM, Uchikawa M, Tsuneyama H, Ogasawara K, Akkøk CA, Daniels G. A new blood group system, RHAG: three antigens resulting from amino acid substitutions in the Rh-associated glycoprotein. Vox Sang. 2010 Feb;98(2):151-9. PMID:19744193 doi:10.1111/j.1423-0410.2009.01243.x
- ↑ Stewart AK, Shmukler BE, Vandorpe DH, Rivera A, Heneghan JF, Li X, Hsu A, Karpatkin M, O'Neill AF, Bauer DE, Heeney MM, John K, Kuypers FA, Gallagher PG, Lux SE, Brugnara C, Westhoff CM, Alper SL. Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG F65S. Am J Physiol Cell Physiol. 2011 Dec;301(6):C1325-43. PMID:21849667 doi:10.1152/ajpcell.00054.2011
- ↑ Genetet S, Ripoche P, Picot J, Bigot S, Delaunay J, Armari-Alla C, Colin Y, Mouro-Chanteloup I. Human RhAG ammonia channel is impaired by the Phe65Ser mutation in overhydrated stomatocytic red cells. Am J Physiol Cell Physiol. 2012 Jan 15;302(2):C419-28. PMID:22012326 doi:10.1152/ajpcell.00092.2011
- ↑ Geyer RR, Parker MD, Toye AM, Boron WF, Musa-Aziz R. Relative CO₂/NH₃ permeabilities of human RhAG, RhBG and RhCG. J Membr Biol. 2013 Dec;246(12):915-26. PMID:24077989 doi:10.1007/s00232-013-9593-0
- ↑ Caner T, Abdulnour-Nakhoul S, Brown K, Islam MT, Hamm LL, Nakhoul NL. Mechanisms of ammonia and ammonium transport by rhesus-associated glycoproteins. Am J Physiol Cell Physiol. 2015 Dec 1;309(11):C747-58. PMID:26354748 doi:10.1152/ajpcell.00085.2015
- ↑ Vallese F, Kim K, Yen LY, Johnston JD, Noble AJ, Cali T, Clarke OB. Architecture of the human erythrocyte ankyrin-1 complex. Nat Struct Mol Biol. 2022 Jul;29(7):706-718. doi: 10.1038/s41594-022-00792-w., Epub 2022 Jul 14. PMID:35835865 doi:https://dx.doi.org/10.1038/s41594-022-00792-w
- ↑ Vallese F, Kim K, Yen LY, Johnston JD, Noble AJ, Cali T, Clarke OB. Architecture of the human erythrocyte ankyrin-1 complex. Nat Struct Mol Biol. 2022 Jul;29(7):706-718. doi: 10.1038/s41594-022-00792-w., Epub 2022 Jul 14. PMID:35835865 doi:https://dx.doi.org/10.1038/s41594-022-00792-w
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