Postila, Pekka; Kaszuba, KarolIST Austria; Kuleta, Patryk; Vattulainen, Ilpo; Sarewicz, Marcin; Osyczka, Artur; Róg, Tomasz
The cytochrome (cyt) bc 1 complex 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 Q i-site of the cyt bc 1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Q i-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 Q i-site.
We wish to thank CSC – IT Centre for Science (Espoo, Finland) for computational resources. For financial support, we wish to thank the Academy of Finland (TR, IV and PAP; Center of Excellence in Biomembrane Research (IV, TR)), the Finnish Doctoral Programme in Computational Sciences (KK), the Sigrid Juselius Foundation (IV), the Paulo Foundation (PAP), and the European Research Council (IV, TR; Advanced Grant project CROWDED-PRO-LIPIDS). AO acknowledges The Wellcome Trust International Senior Research Fellowship.
Postila P, Kaszuba K, Kuleta P, et al. Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports. 2016;6. doi:10.1038/srep33607
Postila, P., Kaszuba, K., Kuleta, P., Vattulainen, I., Sarewicz, M., Osyczka, A., & Róg, T. (2016). Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/srep33607
Postila, Pekka, Karol Kaszuba, Patryk Kuleta, Ilpo Vattulainen, Marcin Sarewicz, Artur Osyczka, and Tomasz Róg. “Atomistic Determinants of Co-Enzyme Q Reduction at the Qi-Site of the Cytochrome Bc1 Complex.” Scientific Reports. Nature Publishing Group, 2016. https://doi.org/10.1038/srep33607.
P. Postila et al., “Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex,” Scientific Reports, vol. 6. Nature Publishing Group, 2016.
Postila P, Kaszuba K, Kuleta P, Vattulainen I, Sarewicz M, Osyczka A, Róg T. 2016. Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports. 6, 33607.
Postila, Pekka, et al. “Atomistic Determinants of Co-Enzyme Q Reduction at the Qi-Site of the Cytochrome Bc1 Complex.” Scientific Reports, vol. 6, 33607, Nature Publishing Group, 2016, doi:10.1038/srep33607.
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