Analysis of a Functional Dimer Model of Ubiquinol Cytochrome c Oxidoreductase.

Abstract:

:Ubiquinol cytochrome c oxidoreductase (bc1 complex) serves as an important electron junction in many respiratory systems. It funnels electrons coming from NADH and ubiquinol to cytochrome c, but it is also capable of producing significant amounts of the free radical superoxide. In situ and in other experimental systems, the enzyme exists as a dimer. But until recently, it was believed to operate as a functional monomer. Here we show that a functional dimer model is capable of explaining both kinetic and superoxide production rate data. The model consists of six electronic states characterized by the number of electrons deposited on the complex. It is fully reversible and strictly adheres to the thermodynamics governing the reactions. A total of nine independent data sets were used to parameterize the model. To explain the data with a consistent set of parameters, it was necessary to incorporate intramonomer Coulombic effects between hemes bL and bH and intermonomer Coulombic effects between bL hemes. The fitted repulsion energies fall within the theoretical range of electrostatic calculations. In addition, model analysis demonstrates that the Q pool is mostly oxidized under normal physiological operation but can switch to a more reduced state when reverse electron transport conditions are in place.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Bazil JN

doi

10.1016/j.bpj.2017.08.018

subject

Has Abstract

pub_date

2017-10-03 00:00:00

pages

1599-1612

issue

7

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(17)30880-9

journal_volume

113

pub_type

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