TY - JOUR
T1 - Mechanism of NH4+ Recruitment and NH3 Transport in Rh Proteins
AU - Baday, Sefer
AU - Orabi, Esam A.
AU - Wang, Shihao
AU - Lamoureux, Guillaume
AU - Bernèche, Simon
N1 - Funding Information:
This work was supported by a grant from the Swiss National Science Foundation to S. Bernèche (SNF Professorship No PP00P3_139205), by an FQRNT Nouveaux chercheurs grant to G.L., and by a PROTEO scholarship and a GEPROM scholarship to E.A.O. Computational resources were provided through a grant from the Swiss National Supercomputing Centre (CSCS) under project ID s421, by sciCORE ( http://scicore.unibas.ch/ ) scientific computing core facility at University of Basel, and through an allocation from Calcul Québec. E.A.O. is currently on leave from Department of Chemistry, Faculty of Science, Assiut University, Egypt.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/8/7
Y1 - 2015/8/7
N2 - Summary In human cells, membrane proteins of the rhesus (Rh) family excrete ammonium and play a role in pH regulation. Based on high-resolution structures, Rh proteins are generally understood to act as NH3 channels. Given that cell membranes are permeable to gases like NH3, the role of such proteins remains a paradox. Using molecular and quantum mechanical calculations, we show that a crystallographically identified site in the RhCG pore actually recruits NH4+, which is found in higher concentration and binds with higher affinity than NH3, increasing the efficiency of the transport mechanism. A proton is transferred from NH4+ to a signature histidine (the only moiety thermodynamically likely to accept a proton) followed by the diffusion of NH3 down the pore. The excess proton is circulated back to the extracellular vestibule through a hydrogen bond network, which involves a highly conserved and functionally important aspartic acid, resulting in the net transport of NH3.
AB - Summary In human cells, membrane proteins of the rhesus (Rh) family excrete ammonium and play a role in pH regulation. Based on high-resolution structures, Rh proteins are generally understood to act as NH3 channels. Given that cell membranes are permeable to gases like NH3, the role of such proteins remains a paradox. Using molecular and quantum mechanical calculations, we show that a crystallographically identified site in the RhCG pore actually recruits NH4+, which is found in higher concentration and binds with higher affinity than NH3, increasing the efficiency of the transport mechanism. A proton is transferred from NH4+ to a signature histidine (the only moiety thermodynamically likely to accept a proton) followed by the diffusion of NH3 down the pore. The excess proton is circulated back to the extracellular vestibule through a hydrogen bond network, which involves a highly conserved and functionally important aspartic acid, resulting in the net transport of NH3.
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U2 - 10.1016/j.str.2015.06.010
DO - 10.1016/j.str.2015.06.010
M3 - Article
C2 - 26190573
AN - SCOPUS:84938740172
SN - 0969-2126
VL - 23
SP - 1550
EP - 1557
JO - Structure
JF - Structure
IS - 8
M1 - 3216
ER -