Redox-linked protonation state changes in cytochrome bc1 identified by Poisson-Boltzmann electrostatics calculations |
| |
Authors: | Astrid R Klingen Carola Hunte |
| |
Institution: | a Structural Biology/Bioinformatics Group, University of Bayreuth, Germany b Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany |
| |
Abstract: | Cytochrome bc1 is a major component of biological energy conversion that exploits an energetically favourable redox reaction to generate a transmembrane proton gradient. Since the mechanistic details of the coupling of redox and protonation reactions in the active sites are largely unresolved, we have identified residues that undergo redox-linked protonation state changes. Structure-based Poisson-Boltzmann/Monte Carlo titration calculations have been performed for completely reduced and completely oxidised cytochrome bc1. Different crystallographically observed conformations of Glu272 and surrounding residues of the cytochrome b subunit in cytochrome bc1 from Saccharomyces cerevisiae have been considered in the calculations. Coenzyme Q (CoQ) has been modelled into the CoQ oxidation site (Qo-site). Our results indicate that both conformational and protonation state changes of Glu272 of cytochrome b may contribute to the postulated gating of CoQ oxidation. The Rieske iron-sulphur cluster could be shown to undergo redox-linked protonation state changes of its histidine ligands in the structural context of the CoQ-bound Qo-site. The proton acceptor role of the CoQ ligands in the CoQ reduction site (Qi-site) is supported by our results. A modified path for proton uptake towards the Qi-site features a cluster of conserved lysine residues in the cytochrome b (Lys228) and cytochrome c1 subunits (Lys288, Lys289, Lys296). The cardiolipin molecule bound close to the Qi-site stabilises protons in this cluster of lysine residues. |
| |
Keywords: | CoQ coenzyme Q ISP iron-sulphur protein FTIR Fourier transform infrared spectroscopy PDB protein data bank (www rcsb org/pdb) HDBT hydroxydioxobenzothiazole PB Poisson Boltzmann MC Monte Carlo CDL cardiolipin Specific residues are denoted by their single letter amino acid code their residue number and a subunit identifier CYB cytochrome b subunit CYC1 cytochrome c1 subunit ISP Rieske iron-sulphur protein subunit SU9 small subunit 9 |
本文献已被 ScienceDirect 等数据库收录! |