Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1complex.
The cytochrome (cyt) bc1complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme's substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Qi-site of the cyt bc1complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Qi-site to facilitate binding of half-protonated semiquinone - a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Qi-site.
Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6A, FI-20520 Turku, Finland.|Department of Chemistry and Biochemistry, University of California San Diego, 92093-0340 San Diego, CA, USA.|Department of Physics, Tampere University of Technology, P.O. Box 692, FI-33101 Tampere, Finland.
Pekka A
PA
Postila
Department of Physics, Tampere University of Technology, P.O. Box 692, FI-33101 Tampere, Finland.|The Institute of Science and Technology, 3400 Klosterneuburg, Austria.
Karol
K
Kaszuba
Department of Molecular Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
Patryk
P
Kuleta
Department of Physics, Tampere University of Technology, P.O. Box 692, FI-33101 Tampere, Finland.|Department of Physics, University of Helsinki, P.O. Box 64, FI-00014, Helsinki, Finland.|MEMPHYS - Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark.
Ilpo
I
Vattulainen
Department of Molecular Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
Marcin
M
Sarewicz
Department of Molecular Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
Artur
A
Osyczka
Department of Physics, Tampere University of Technology, P.O. Box 692, FI-33101 Tampere, Finland.|Department of Physics, University of Helsinki, P.O. Box 64, FI-00014, Helsinki, Finland.
Tomasz
T
Róg
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