Mutations in a conserved loop in the PSST subunit of respiratory complex I affect ubiquinone binding and dynamics

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Yoga , E G , Haapanen , O , Wittig , I , Siegmund , K , Sharma , V & Zickermann , V 2019 , ' Mutations in a conserved loop in the PSST subunit of respiratory complex I affect ubiquinone binding and dynamics ' , Biochimica et Biophysica Acta. Bioenergetics , vol. 1860 , no. 7 , pp. 573-581 . https://doi.org/10.1016/j.bbabio.2019.06.006

Title: Mutations in a conserved loop in the PSST subunit of respiratory complex I affect ubiquinone binding and dynamics
Author: Yoga, Etienne Galemou; Haapanen, Outi; Wittig, Ilka; Siegmund, Karin; Sharma, Vivek; Zickermann, Volker
Contributor: University of Helsinki, Materials Physics
University of Helsinki, Materials Physics
Date: 2019-07-01
Language: eng
Number of pages: 9
Belongs to series: Biochimica et Biophysica Acta. Bioenergetics
ISSN: 0005-2728
URI: http://hdl.handle.net/10138/304764
Abstract: Respiratory complex I catalyses the reduction of ubiquinone (Q) from NADH coupled to proton pumping across the inner membrane of mitochondria. The electrical charging of the inner mitochondrial membrane drives the synthesis of ATP, which is used to power biochemical reactions of the cell. The recent surge in structural data on complex I from bacteria and mitochondria have contributed to significant understanding of its molecular architecture. However, despite these accomplishments, the role of various subdomains in redox-coupled proton pumping remains entirely unclear. In this work, we have mutated conserved residues in the loop of the PSST subunit that faces the similar to 30 angstrom long unique Q-binding tunnel of respiratory complex I. The data show a drastic decrease in Q reductase activity upon mutating several residues despite full assembly of the complex. In-silico modeling and multiple microsecond long molecular dynamics simulations of wild-type and enzyme variants with exchanges of conserved arginine residues revealed remarkable ejection of the bound Q from the site near terminal electron donor N2. Based on experiments and long-time scale molecular simulations, we identify microscopic elements that dynamically control the diffusion of Q and are central to redox-coupled proton pumping in respiratory complex I.
Subject: Cell respiration
Proton pumping
Electron transfer
Redox-coupled proton pumping
Quinone dynamics
MOLECULAR-DYNAMICS
CRYSTAL-STRUCTURE
YARROWIA-LIPOLYTICA
MEMBRANE DOMAIN
QUINONE BINDING
OXIDOREDUCTASE
CHARMM
ND1
PURIFICATION
ARCHITECTURE
116 Chemical sciences
114 Physical sciences
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