Function of human Rh based on structure of RhCG at 2.1 A.
In humans, NH(3) transport across cell membranes is facilitated by the Rh (rhesus) family of proteins. Human Rh C glycoprotein (RhCG) forms a trimeric complex that plays an essential role in ammonia excretion and renal pH regulation. The X-ray crystallographic structure of human RhCG, determined at 2.1 A resolution, reveals the mechanism of ammonia transport. Each monomer contains 12 transmembrane helices, one more than in the bacterial homologs. Reconstituted into proteoliposomes, RhCG conducts NH(3) to raise internal pH. Models of the erythrocyte Rh complex based on our RhCG structure suggest that the erythrocytic Rh complex is composed of stochastically assembled heterotrimers of RhAG, RhD, and RhCE.
Gruswitz
Franz
F
Department of Biochemistry and Biophysics, S412C Genentech Hall, Center for the Structure of Membrane Proteins, and Membrane Protein Expression Center, University of California, San Francisco, CA 94158, USA.
Chaudhary
Sarika
S
Ho
Joseph D
JD
Schlessinger
Avner
A
Pezeshki
Bobak
B
Ho
Chi-Min
CM
Sali
Andrej
A
Westhoff
Connie M
CM
Stroud
Robert M
RM
D000641:Ammonia / Q000378:metabolism; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D018360:Crystallography, X-Ray; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012204:Rh-Hr Blood-Group System / Q000737:chemistry* / Q000378:metabolism*
D027682:Cation Transport Proteins; D008562:Membrane Glycoproteins; C413213:RHCG protein, human; D012204:Rh-Hr Blood-Group System; D000641:Ammonia
Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
15299374
J Biol Chem. 2002 Apr 12;277(15):12499-502
11861637
Transfus Clin Biol. 2006 Mar-Apr;13(1-2):132-8
16563829
J Mol Biol. 1993 Dec 5;234(3):779-815
8254673
Physiol Rev. 1989 Jan;69(1):179-249
2643123
Am J Physiol Renal Physiol. 2004 Jan;286(1):F161-9
12965893
Nature. 2008 Nov 20;456(7220):339-43
19020613
Am J Physiol Renal Physiol. 2006 Feb;290(2):F397-408
16144966
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
11517324
Int J Biochem Cell Biol. 2005 Jun;37(6):1151-61
15778079
BMC Struct Biol. 2008 Nov 14;8:49
19014592
JAMA. 1984 Mar 9;251(10):1316-7
6366259
J Biol Chem. 1992 Mar 15;267(8):5569-74
1544931
J Biol Chem. 2004 Apr 16;279(16):15975-83
14761968
J Am Soc Nephrol. 2007 May;18(5):1408-18
17409310
Am J Physiol Renal Physiol. 2006 Feb;290(2):F297-305
16131648
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7769-73
12032358
Science. 2004 Sep 10;305(5690):1587-94
15361618
Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
15299926
J Biol Chem. 1994 Mar 4;269(9):6417-23
8119991
Protein Sci. 2006 Nov;15(11):2507-24
17075131
J Am Soc Nephrol. 1991 May;1(11):1193-203
1932632
Physiol Rev. 1981 Apr;61(2):296-434
7012859
Biochemistry. 1993 Mar 16;32(10):2459-68
8383520
Biochem J. 2005 Aug 15;390(Pt 1):215-22
15876187
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19279-84
18040042
J Biol Chem. 2006 Dec 22;281(51):39492-8
17040913
Trends Biochem Sci. 1997 Dec;22(12):460-1
9433124
Curr Genet. 2006 Jun;49(6):364-74
16477434
Proc Natl Acad Sci U S A. 2004 May 18;101(20):7787-92
15096599
Blood. 1991 Nov 15;78(10):2747-52
1824267
Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1445-50
11567158
Am J Physiol. 1994 Dec;267(6 Pt 2):F952-64
7810703
Am J Physiol Renal Physiol. 2009 Jun;296(6):F1279-90
19357182
Transfus Clin Biol. 2006 Mar-Apr;13(1-2):128-31
16580862
Transfus Clin Biol. 2006 Mar-Apr;13(1-2):139-46
16564724
Physiol Rev. 2004 Oct;84(4):1263-314
15383652
Am J Physiol Renal Physiol. 2009 Jun;296(6):F1364-75
19321595
J Am Soc Nephrol. 2003 Mar;14(3):545-54
12595489
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
15572765
J Am Soc Nephrol. 2006 Oct;17(10):2670-9
16928804
Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17090-5
15563598
Pflugers Arch. 2009 May;458(1):137-56
19277700
Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):14994-9
16214888
Nat Genet. 2000 Nov;26(3):341-4
11062476
Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17222-7
15572441
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3926-31
11891327
Acta Crystallogr D Biol Crystallogr. 2004 Mar;60(Pt 3):432-8
14993666
Am J Physiol Renal Physiol. 2003 Feb;284(2):F323-37
12388412
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13413-8
12370422
Am J Physiol Renal Physiol. 2009 Mar;296(3):F543-55
19129254
Nucleic Acids Res. 2002 Jan 1;30(1):255-9
11752309
J Biol Chem. 2004 Mar 5;279(10):8530-8
14668330
Am J Physiol. 1987 Oct;253(4 Pt 2):F595-605
3310662
J Am Soc Nephrol. 2002 Aug;13(8):2160-70
12138150
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19303-8
18032606
Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5406-11
19273840