Towards Molecular Understanding of the Functional Role of UbiJ-UbiK<sub>2</sub> 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 <i>E. coli</i> within a multiprotein co...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10323 |
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| author | Romain Launay Elin Teppa Carla Martins Sophie S. Abby Fabien Pierrel Isabelle André Jérémy Esque |
| author_facet | Romain Launay Elin Teppa Carla Martins Sophie S. Abby Fabien Pierrel Isabelle André Jérémy Esque |
| author_sort | Romain Launay |
| collection | DOAJ |
| 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 <i>E. coli</i> 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<sub>2</sub> 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<sub>2</sub> heterotrimer. Our data show that UbiJ-UbiK<sub>2</sub> interacts closely with the membrane and suggests possible pathways to enable the release of UQ into the membrane. This study highlights the UbiJ-UbiK<sub>2</sub> 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<sub>8</sub> and its release into the membrane of <i>E. coli</i>. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:47:19Z |
| publishDate | 2022-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-02aeb8cbdcab45bc8a235001ec6858f12023-11-23T16:39:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181032310.3390/ijms231810323Towards Molecular Understanding of the Functional Role of UbiJ-UbiK<sub>2</sub> Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling StudiesRomain Launay0Elin Teppa1Carla Martins2Sophie S. Abby3Fabien Pierrel4Isabelle André5Jérémy Esque6Toulouse Biotechnology Institute, TBI, Université de Toulouse, CNRS, INRAE, INSA, 31077 Toulouse, FranceToulouse Biotechnology Institute, TBI, Université de Toulouse, CNRS, INRAE, INSA, 31077 Toulouse, FranceToulouse Biotechnology Institute, TBI, Université de Toulouse, CNRS, INRAE, INSA, 31077 Toulouse, FranceUniv. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, FranceUniv. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, FranceToulouse Biotechnology Institute, TBI, Université de Toulouse, CNRS, INRAE, INSA, 31077 Toulouse, FranceToulouse Biotechnology Institute, TBI, Université de Toulouse, CNRS, INRAE, INSA, 31077 Toulouse, FranceUbiquinone (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 <i>E. coli</i> 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<sub>2</sub> 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<sub>2</sub> heterotrimer. Our data show that UbiJ-UbiK<sub>2</sub> interacts closely with the membrane and suggests possible pathways to enable the release of UQ into the membrane. This study highlights the UbiJ-UbiK<sub>2</sub> 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<sub>8</sub> and its release into the membrane of <i>E. coli</i>.https://www.mdpi.com/1422-0067/23/18/10323ubiquinoneMD simulationsAlphafold2molecular modellingMartini 3 force fieldperipheral membrane protein |
| spellingShingle | Romain Launay Elin Teppa Carla Martins Sophie S. Abby Fabien Pierrel Isabelle André Jérémy Esque Towards Molecular Understanding of the Functional Role of UbiJ-UbiK<sub>2</sub> Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies International Journal of Molecular Sciences ubiquinone MD simulations Alphafold2 molecular modelling Martini 3 force field peripheral membrane protein |
| title | Towards Molecular Understanding of the Functional Role of UbiJ-UbiK<sub>2</sub> Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies |
| title_full | Towards Molecular Understanding of the Functional Role of UbiJ-UbiK<sub>2</sub> Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies |
| title_fullStr | Towards Molecular Understanding of the Functional Role of UbiJ-UbiK<sub>2</sub> Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies |
| title_full_unstemmed | Towards Molecular Understanding of the Functional Role of UbiJ-UbiK<sub>2</sub> Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies |
| title_short | Towards Molecular Understanding of the Functional Role of UbiJ-UbiK<sub>2</sub> Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies |
| title_sort | towards molecular understanding of the functional role of ubij ubik sub 2 sub complex in ubiquinone biosynthesis by multiscale molecular modelling studies |
| topic | ubiquinone MD simulations Alphafold2 molecular modelling Martini 3 force field peripheral membrane protein |
| url | https://www.mdpi.com/1422-0067/23/18/10323 |
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