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Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410
Mycobacterium tuberculosis is protected from antibiotic therapy by a multi-layered hydrophobic cell envelope. Major facilitator superfamily (MFS) transporter Rv1410 and the periplasmic lipoprotein LprG are involved in transport of triacylglycerides (TAGs) that seal the mycomembrane. Here, we report...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576003/ https://www.ncbi.nlm.nih.gov/pubmed/37833269 http://dx.doi.org/10.1038/s41467-023-42073-0 |
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author | Remm, Sille De Vecchis, Dario Schöppe, Jendrik Hutter, Cedric A. J. Gonda, Imre Hohl, Michael Newstead, Simon Schäfer, Lars V. Seeger, Markus A. |
author_facet | Remm, Sille De Vecchis, Dario Schöppe, Jendrik Hutter, Cedric A. J. Gonda, Imre Hohl, Michael Newstead, Simon Schäfer, Lars V. Seeger, Markus A. |
author_sort | Remm, Sille |
collection | PubMed |
description | Mycobacterium tuberculosis is protected from antibiotic therapy by a multi-layered hydrophobic cell envelope. Major facilitator superfamily (MFS) transporter Rv1410 and the periplasmic lipoprotein LprG are involved in transport of triacylglycerides (TAGs) that seal the mycomembrane. Here, we report a 2.7 Å structure of a mycobacterial Rv1410 homologue, which adopts an outward-facing conformation and exhibits unusual transmembrane helix 11 and 12 extensions that protrude ~20 Å into the periplasm. A small, very hydrophobic cavity suitable for lipid transport is constricted by a functionally important ion-lock likely involved in proton coupling. Combining mutational analyses and MD simulations, we propose that TAGs are extracted from the core of the inner membrane into the central cavity via lateral clefts present in the inward-facing conformation. The functional role of the periplasmic helix extensions is to channel the extracted TAG into the lipid binding pocket of LprG. |
format | Online Article Text |
id | pubmed-10576003 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105760032023-10-15 Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410 Remm, Sille De Vecchis, Dario Schöppe, Jendrik Hutter, Cedric A. J. Gonda, Imre Hohl, Michael Newstead, Simon Schäfer, Lars V. Seeger, Markus A. Nat Commun Article Mycobacterium tuberculosis is protected from antibiotic therapy by a multi-layered hydrophobic cell envelope. Major facilitator superfamily (MFS) transporter Rv1410 and the periplasmic lipoprotein LprG are involved in transport of triacylglycerides (TAGs) that seal the mycomembrane. Here, we report a 2.7 Å structure of a mycobacterial Rv1410 homologue, which adopts an outward-facing conformation and exhibits unusual transmembrane helix 11 and 12 extensions that protrude ~20 Å into the periplasm. A small, very hydrophobic cavity suitable for lipid transport is constricted by a functionally important ion-lock likely involved in proton coupling. Combining mutational analyses and MD simulations, we propose that TAGs are extracted from the core of the inner membrane into the central cavity via lateral clefts present in the inward-facing conformation. The functional role of the periplasmic helix extensions is to channel the extracted TAG into the lipid binding pocket of LprG. Nature Publishing Group UK 2023-10-13 /pmc/articles/PMC10576003/ /pubmed/37833269 http://dx.doi.org/10.1038/s41467-023-42073-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Remm, Sille De Vecchis, Dario Schöppe, Jendrik Hutter, Cedric A. J. Gonda, Imre Hohl, Michael Newstead, Simon Schäfer, Lars V. Seeger, Markus A. Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410 |
title | Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410 |
title_full | Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410 |
title_fullStr | Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410 |
title_full_unstemmed | Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410 |
title_short | Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410 |
title_sort | structural basis for triacylglyceride extraction from mycobacterial inner membrane by mfs transporter rv1410 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576003/ https://www.ncbi.nlm.nih.gov/pubmed/37833269 http://dx.doi.org/10.1038/s41467-023-42073-0 |
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