The ubiquinol cytochrome c oxidoreductase (cytochrome bc1 complex) plays a central role in electron transport chains of bacteria, mitochondria and chloroplasts, converting redox free energy into a proton gradient used to drive the cell's metabolism through ATP synthesis. This complex catalyzes the oxidation of ubiquinol in the membrane, the reduction of cytochrome c and the translocation of protons across the membrane [97]. All bc1 complexes contain three essential sub-units to which the prosthetic groups are bound: a cytochrome (cyt) b with high- and low-potential hemes bH and bL, an iron sulfur protein (ISP) containing a 2Fe2S center, and a cytochrome c1 with another heme group. The catalytic mechanism involves two catalytic sites for oxidation (Oo site) or reduction (Oi site) of the quinones. The crystal structures of several mitochondrial bc1 complexes with and without an inhibitor (stigmatellin) bound at the Oo site became available during the past year [98, 99]. In the structure with stigmatellin bound, part of the ISP domain is turned with respect to its position in the structure without the inhibitor [99]. This suggests that the electron transfer path from the Oo site to cyt c1 involves a substantial movement of the ISP. Our collaborator, A. R. Crofts, provided us with crystal structures of chicken heart mitochondria bc1 complexes, with and without the inhibitor bound at the Oo site [99]. Comparison of these two structures revealed the axis of rotation of the iron sulfur protein (ISP) mobile head and the angle of rotation. We have prepared two systems consisting of the cytochrome b, cytochrome c1 and ISP domains of the two structures for equilibration. We investigate the mechanism governing the rotation of the ISP head by means of Steered Molecular Dynamic (SMD) simulations [3-8, 100]. In the simulations, external forces have to be applied to the ISP to provide an appropriate torque inducing the rotation. We are mainly interested in revealing the geometrical constraints imposed on the movement of the ISP head by the other sub-units of the bc1 complex. We will simulate the rotation of the ISP head in the presence of cyt b and cyt c1 sub-units by using SMD to induce the rotation. This simulation will provide the information on whether the motion of the ISP head is unconstrained or it involves molecular interactions that may induce or prevent the rotation. The latter case may indicate mutations that alter the rate of the catalytic reaction.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR005969-10
Application #
6220796
Study Section
Project Start
1999-08-01
Project End
2000-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Shim, Jiwook; Banerjee, Shouvik; Qiu, Hu et al. (2017) Detection of methylation on dsDNA using nanopores in a MoS2 membrane. Nanoscale 9:14836-14845
Wolfe, Aaron J; Si, Wei; Zhang, Zhengqi et al. (2017) Quantification of Membrane Protein-Detergent Complex Interactions. J Phys Chem B 121:10228-10241
Decker, Karl; Page, Martin; Aksimentiev, Aleksei (2017) Nanoscale Ion Pump Derived from a Biological Water Channel. J Phys Chem B 121:7899-7906
Radak, Brian K; Chipot, Christophe; Suh, Donghyuk et al. (2017) Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems. J Chem Theory Comput 13:5933-5944
Sun, Chang; Taguchi, Alexander T; Vermaas, Josh V et al. (2016) Q-Band Electron-Nuclear Double Resonance Reveals Out-of-Plane Hydrogen Bonds Stabilize an Anionic Ubisemiquinone in Cytochrome bo3 from Escherichia coli. Biochemistry 55:5714-5725
Belkin, Maxim; Aksimentiev, Aleksei (2016) Molecular Dynamics Simulation of DNA Capture and Transport in Heated Nanopores. ACS Appl Mater Interfaces 8:12599-608
Poudel, Kumud R; Dong, Yongming; Yu, Hang et al. (2016) A time course of orchestrated endophilin action in sensing, bending, and stabilizing curved membranes. Mol Biol Cell 27:2119-32
Vermaas, Josh V; Taguchi, Alexander T; Dikanov, Sergei A et al. (2015) Redox potential tuning through differential quinone binding in the photosynthetic reaction center of Rhodobacter sphaeroides. Biochemistry 54:2104-16
Belkin, Maxim; Chao, Shu-Han; Jonsson, Magnus P et al. (2015) Plasmonic Nanopores for Trapping, Controlling Displacement, and Sequencing of DNA. ACS Nano 9:10598-611
Shen, Rong; Han, Wei; Fiorin, Giacomo et al. (2015) Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments. PLoS Comput Biol 11:e1004368

Showing the most recent 10 out of 371 publications