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 - 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 -