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Redox Membrane Proteins

One of the current challenges in the research on electronic transport phenomena in biology is to understand how electron transfer steps are intercalated within complex biochemical machineries. Indeed, the transfer of an electron from one redox cofactor to another induces rearrangements in the environment occurring over timescales ranging from femtoseconds to microseconds, which overlap significantly with those of other biological processes. The case of redox membrane proteins is a particularly interesting example that has so far been only minimally addressed by theoretical approaches.

Following the publication of the first experimental structure in 2017, we initiated the study of electron transfer catalysis across membranes by NADPH oxidases (NOX). This involves the first molecular dynamics simulations of a NOX system in a membrane environment, with a theoretical estimation of the kinetic and thermodynamic parameters between the heme cofactors contained within the membrane [Wu2021]. This exploratory work led to the emergence of a collaborative project with the CPSysBio group, LBT, and the Institute of Integrative Biology of the Cell (I2BC, Paris Saclay), and the recruitment of a PhD student, Baptiste Etcheverry (2022-).

On another front, we have started a project on Cytochrome bd in collaboration with the University of Strasbourg. These bacterial proteins catalyze the reduction of small molecules to protect these organisms from oxidative stress. Our goal is to understand the control of the thermodynamics of electron transfer between the three hemes embedded in these proteins, whose redox potentials vary significantly from one species to another.

NADPH oxidases (NOX) catalyze, as part of the immune defense, the production of reactive oxygen species (e.g., O2•-) through a series of electron transfers from NADPH on one side of the membrane to a molecule of dioxygen on the other side.

Collaborations

Laura Baciou, Tania Bizouarn, and Chantal Houée-Lévin (CPSysBio, ICP), Marc Baaden (LBT/IBPC, Paris), Pavel Müller (I2BC, Paris-Saclay), Petra Hellwig, and Frédéric Melin (LBS, U. Strasbourg)