TY - JOUR
T1 - Hydrogen bond network analysis reveals the pathway for the proton transfer in the E-channel of T. thermophilus Complex I
AU - Khaniya, Umesh
AU - Gupta, Chitrak
AU - Cai, Xiuhong
AU - Mao, Junjun
AU - Kaur, Divya
AU - Zhang, Yingying
AU - Singharoy, Abhishek
AU - Gunner, M. R.
N1 - Funding Information:
MRG and UK acknowledge funding from National Science Foundation (grant number MCB-1519640 ). AS acknowledges NSF ( MCB-1942763 ). AS and CG acknowledge start-up funds from the SMS and CASD at Arizona State University , and the resources of the OLCF at the Oak Ridge National Laboratory, which is supported by the Office of Science at DOE under Contract No. DE-AC05-00OR22725, made available via the INCITE program.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Complex I, NADH-ubiquinone oxidoreductase, is the first enzyme in the mitochondrial and bacterial aerobic respiratory chain. It pumps four protons through four transiently open pathways from the high pH, negative, N-side of the membrane to the positive, P-side driven by the exergonic transfer of electrons from NADH to a quinone. Three protons transfer through subunits descended from antiporters, while the fourth, E-channel is unique. The path through the E-channel is determined by a network analysis of hydrogen bonded pathways obtained by Monte Carlo sampling of protonation states, polar hydrogen orientation and water occupancy. Input coordinates are derived from molecular dynamics trajectories comparing oxidized, reduced (dihydro) and no menaquinone-8 (MQ). A complex proton transfer path from the N- to the P-side is found consisting of six clusters of highly connected hydrogen-bonded residues. The network connectivity depends on the presence of quinone and its redox state, supporting a role for this cofactor in coupling electron and proton transfers. The N-side is more organized with MQ-bound complex I facilitating proton entry, while the P-side is more connected in the apo-protein, facilitating proton exit. Subunit Nqo8 forms the core of the E channel; Nqo4 provides the N-side entry, Nqo7 and then Nqo10 join the pathway in the middle, while Nqo11 contributes to the P-side exit.
AB - Complex I, NADH-ubiquinone oxidoreductase, is the first enzyme in the mitochondrial and bacterial aerobic respiratory chain. It pumps four protons through four transiently open pathways from the high pH, negative, N-side of the membrane to the positive, P-side driven by the exergonic transfer of electrons from NADH to a quinone. Three protons transfer through subunits descended from antiporters, while the fourth, E-channel is unique. The path through the E-channel is determined by a network analysis of hydrogen bonded pathways obtained by Monte Carlo sampling of protonation states, polar hydrogen orientation and water occupancy. Input coordinates are derived from molecular dynamics trajectories comparing oxidized, reduced (dihydro) and no menaquinone-8 (MQ). A complex proton transfer path from the N- to the P-side is found consisting of six clusters of highly connected hydrogen-bonded residues. The network connectivity depends on the presence of quinone and its redox state, supporting a role for this cofactor in coupling electron and proton transfers. The N-side is more organized with MQ-bound complex I facilitating proton entry, while the P-side is more connected in the apo-protein, facilitating proton exit. Subunit Nqo8 forms the core of the E channel; Nqo4 provides the N-side entry, Nqo7 and then Nqo10 join the pathway in the middle, while Nqo11 contributes to the P-side exit.
KW - Complex I
KW - Grand Canonical Monte Carlo Simulations
KW - Hydrogen bond network
KW - Proton pumping
KW - Proton transfer
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U2 - 10.1016/j.bbabio.2020.148240
DO - 10.1016/j.bbabio.2020.148240
M3 - Article
C2 - 32531220
AN - SCOPUS:85086652296
SN - 0005-2728
VL - 1861
JO - Biochimica et Biophysica Acta - Bioenergetics
JF - Biochimica et Biophysica Acta - Bioenergetics
IS - 10
M1 - 148240
ER -