Dataset Information

Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I.

ABSTRACT: Respiratory complex I performs the reduction of quinone (Q) to quinol (QH2) and pumps protons across the membrane. Structural data on complex I have provided spectacular insights into the electron and proton transfer paths, as well as into the long (~30 Å) and unique substrate binding channel. However, due to missing structural information on Q binding modes, it remains unclear how Q reduction drives long range (~20 nm) redox-coupled proton pumping in complex I. Here we applied multiscale computational approaches to study the dynamics and redox chemistry of Q and QH2. Based on tens of microseconds of atomistic molecular dynamics (MD) simulations of bacterial and mitochondrial complex I, we find that the dynamics of Q is remarkably rapid and it diffuses from the N2 binding site to another stable site near the entrance of the Q channel in microseconds. Analysis of simulation trajectories also reveal the presence of yet another Q binding site 25-30 Å from the N2 center, which is in remarkable agreement with the electron density observed in recent cryo electron microscopy structure of complex I from Yarrowia lipolytica. Quantum chemical computations on the two Q binding sites closer to the entrance of the Q tunnel reveal redox-coupled protonation reactions that may be important in driving the proton pump of complex I.

SUBMITTER: Haapanen O

PROVIDER: S-EPMC6465577 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I.

Haapanen Outi O Djurabekova Amina A Sharma Vivek V

Frontiers in chemistry 20190409

Respiratory complex I performs the reduction of quinone (Q) to quinol (QH<sub>2</sub>) and pumps protons across the membrane. Structural data on complex I have provided spectacular insights into the electron and proton transfer paths, as well as into the long (~30 Å) and unique substrate binding channel. However, due to missing structural information on Q binding modes, it remains unclear how Q reduction drives long range (~20 nm) redox-coupled proton pumping in complex I. Here we applied multis ...[more]

PMID: 31024903

Similar Datasets

Project description:Monotopic membrane-bound flavoproteins, sulfide:quinone oxidoreductases (SQRs), have a variety of physiological functions, including sulfide detoxification. SQR enzymes are classified into six groups. SQRs use the flavin adenine dinucleotide (FAD) cofactor to transfer electrons from sulfide to quinone. A type VI SQR of the photosynthetic purple sulfur bacterium, Thiocapsa roseopersicina (TrSqrF), has been previously characterized, and the mechanism of sulfide oxidation has been proposed. This paper reports the characterization of quinone binding site (QBS) of TrSqrF composed of conserved aromatic and apolar amino acids. Val331, Ile333, and Phe366 were identified near the benzoquinone ring of enzyme-bound decylubiquinone (dUQ) using the TrSqrF homology model. In silico analysis revealed that Val331 and Ile333 alternately connected with the quinone head group via hydrogen bonds, and Phe366 and Trp369 bound the quinones via hydrophobic interactions. TrSqrF variants containing alanine (V331A, I333A, F366A) and aromatic amino acid (V331F, I333F, F366Y), as well as a C-terminal α-helix deletion (CTD) mutant were generated. These amino acids are critical for quinone binding and, thus, catalysis. Spectroscopic analyses proved that all mutants contained FAD. I333F replacement resulted in the lack of the charge transfer complex. In summary, the interactions described above maintain the quinone molecule's head in an optimal position for direct electron transfer from FAD. Surprisingly, the CTD mutant retained a relatively high level of specific activity while remaining membrane-anchored. This is a unique study because it focuses on the QBS and the oxidative stage of a type VI sulfide-dependent quinone reduction. KEY POINTS: • V331, I333, F366, and W369 were shown to interact with decylubiquinone in T. roseopersicina SqrF • These amino acids are involved in proper positioning of quinones next to FAD • I333 is essential in formation of a charge transfer complex from FAD to quinone.

Dataset Information

Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I.

Publications

Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets