Function of human Rh based on structure of RhCG at 2.1 Å

Abstract

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 Å 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.ammonia channel | comparative modeling | membrane protein | rhesus factor | X-ray structure

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

“…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).…”

The TORC1 effector kinase Npr1 fine tunes the inherent activity of the Mep2 ammonium transport protein

“…These belong to the Mep-Amt-Rh protein superfamily, including the human Rhesus (Rh) blood group antigens and mediating ammonium transport in organisms as distant as bacteria and mammals [12][13][14] . Available x-ray structures of Mep-Amt-Rh proteins reveal a similar trimeric fold, with a conducting pore crossing each of the three monomers [15][16][17][18][19][20] . One monomer comprises 11 or 12 helices and is prolonged by a cytosolic C-terminal extension of variable length.…”

De la découverte des transporteurs d’ammonium Mep-Amt microbiens aux facteurs Rhésus humains

“…Les membres de la famille Rh seraient structurés en 12 segments transmembranaires, bien que la protéine Rh50 de la bactérie Nitrosomonas europaea ait été, elle, cristallisée dans une configuration à 11 segments transmembranaires [23,24]. Les structures cristallines des protéines Rh50 de N. europaea [23,24] et RhCG humaine [25] sont très similaires à celles des Amt cristallisées. Cependant, en accord avec la plupart des études électrophy-siologiques indiquant un transport électroneutre par les protéines Rh [26][27][28], les données cristallographiques suggèrent une reconnaissance et une translocation de la forme neutre NH 3 .…”