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Towards Molecular Understanding of the Functional Role of UbiJ-UbiK(2) Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies

Ubiquinone (UQ) is a polyisoprenoid lipid found in the membranes of bacteria and eukaryotes. UQ has important roles, notably in respiratory metabolisms which sustain cellular bioenergetics. Most steps of UQ biosynthesis take place in the cytosol of E. coli within a multiprotein complex called the Ub...

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Autores principales: Launay, Romain, Teppa, Elin, Martins, Carla, Abby, Sophie S., Pierrel, Fabien, André, Isabelle, Esque, Jérémy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499169/
https://www.ncbi.nlm.nih.gov/pubmed/36142227
http://dx.doi.org/10.3390/ijms231810323
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author Launay, Romain
Teppa, Elin
Martins, Carla
Abby, Sophie S.
Pierrel, Fabien
André, Isabelle
Esque, Jérémy
author_facet Launay, Romain
Teppa, Elin
Martins, Carla
Abby, Sophie S.
Pierrel, Fabien
André, Isabelle
Esque, Jérémy
author_sort Launay, Romain
collection PubMed
description Ubiquinone (UQ) is a polyisoprenoid lipid found in the membranes of bacteria and eukaryotes. UQ has important roles, notably in respiratory metabolisms which sustain cellular bioenergetics. Most steps of UQ biosynthesis take place in the cytosol of E. coli within a multiprotein complex called the Ubi metabolon, that contains five enzymes and two accessory proteins, UbiJ and UbiK. The SCP2 domain of UbiJ was proposed to bind the hydrophobic polyisoprenoid tail of UQ biosynthetic intermediates in the Ubi metabolon. How the newly synthesised UQ might be released in the membrane is currently unknown. In this paper, we focused on better understanding the role of the UbiJ-UbiK(2) heterotrimer forming part of the metabolon. Given the difficulties to gain functional insights using biophysical techniques, we applied a multiscale molecular modelling approach to study the UbiJ-UbiK(2) heterotrimer. Our data show that UbiJ-UbiK(2) interacts closely with the membrane and suggests possible pathways to enable the release of UQ into the membrane. This study highlights the UbiJ-UbiK(2) complex as the likely interface between the membrane and the enzymes of the Ubi metabolon and supports that the heterotrimer is key to the biosynthesis of UQ(8) and its release into the membrane of E. coli.
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spelling pubmed-94991692022-09-23 Towards Molecular Understanding of the Functional Role of UbiJ-UbiK(2) Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies Launay, Romain Teppa, Elin Martins, Carla Abby, Sophie S. Pierrel, Fabien André, Isabelle Esque, Jérémy Int J Mol Sci Article Ubiquinone (UQ) is a polyisoprenoid lipid found in the membranes of bacteria and eukaryotes. UQ has important roles, notably in respiratory metabolisms which sustain cellular bioenergetics. Most steps of UQ biosynthesis take place in the cytosol of E. coli within a multiprotein complex called the Ubi metabolon, that contains five enzymes and two accessory proteins, UbiJ and UbiK. The SCP2 domain of UbiJ was proposed to bind the hydrophobic polyisoprenoid tail of UQ biosynthetic intermediates in the Ubi metabolon. How the newly synthesised UQ might be released in the membrane is currently unknown. In this paper, we focused on better understanding the role of the UbiJ-UbiK(2) heterotrimer forming part of the metabolon. Given the difficulties to gain functional insights using biophysical techniques, we applied a multiscale molecular modelling approach to study the UbiJ-UbiK(2) heterotrimer. Our data show that UbiJ-UbiK(2) interacts closely with the membrane and suggests possible pathways to enable the release of UQ into the membrane. This study highlights the UbiJ-UbiK(2) complex as the likely interface between the membrane and the enzymes of the Ubi metabolon and supports that the heterotrimer is key to the biosynthesis of UQ(8) and its release into the membrane of E. coli. MDPI 2022-09-07 /pmc/articles/PMC9499169/ /pubmed/36142227 http://dx.doi.org/10.3390/ijms231810323 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Launay, Romain
Teppa, Elin
Martins, Carla
Abby, Sophie S.
Pierrel, Fabien
André, Isabelle
Esque, Jérémy
Towards Molecular Understanding of the Functional Role of UbiJ-UbiK(2) Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies
title Towards Molecular Understanding of the Functional Role of UbiJ-UbiK(2) Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies
title_full Towards Molecular Understanding of the Functional Role of UbiJ-UbiK(2) Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies
title_fullStr Towards Molecular Understanding of the Functional Role of UbiJ-UbiK(2) Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies
title_full_unstemmed Towards Molecular Understanding of the Functional Role of UbiJ-UbiK(2) Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies
title_short Towards Molecular Understanding of the Functional Role of UbiJ-UbiK(2) Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies
title_sort towards molecular understanding of the functional role of ubij-ubik(2) complex in ubiquinone biosynthesis by multiscale molecular modelling studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499169/
https://www.ncbi.nlm.nih.gov/pubmed/36142227
http://dx.doi.org/10.3390/ijms231810323
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