Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.

The mycobacterial membrane protein large 3 (MmpL3) transporter is essential and required for shuttling the lipid trehalose monomycolate (TMM), a precursor of mycolic acid (MA)-containing trehalose dimycolate (TDM) and mycolyl arabinogalactan peptidoglycan (mAGP), in Mycobacterium species, including...

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Autores principales:	Chih-Chia Su, Philip A Klenotic, Meng Cui, Meinan Lyu, Christopher E Morgan, Edward W Yu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c854280c53b8409988242410fd435240
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spelling	oai:doaj.org-article:c854280c53b8409988242410fd4352402021-12-02T19:54:39ZStructures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.1544-91731545-788510.1371/journal.pbio.3001370https://doaj.org/article/c854280c53b8409988242410fd4352402021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001370https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The mycobacterial membrane protein large 3 (MmpL3) transporter is essential and required for shuttling the lipid trehalose monomycolate (TMM), a precursor of mycolic acid (MA)-containing trehalose dimycolate (TDM) and mycolyl arabinogalactan peptidoglycan (mAGP), in Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium smegmatis. However, the mechanism that MmpL3 uses to facilitate the transport of fatty acids and lipidic elements to the mycobacterial cell wall remains elusive. Here, we report 7 structures of the M. smegmatis MmpL3 transporter in its unbound state and in complex with trehalose 6-decanoate (T6D) or TMM using single-particle cryo-electron microscopy (cryo-EM) and X-ray crystallography. Combined with calculated results from molecular dynamics (MD) and target MD simulations, we reveal a lipid transport mechanism that involves a coupled movement of the periplasmic domain and transmembrane helices of the MmpL3 transporter that facilitates the shuttling of lipids to the mycobacterial cell wall.Chih-Chia SuPhilip A KlenoticMeng CuiMeinan LyuChristopher E MorganEdward W YuPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 8, p e3001370 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Chih-Chia Su Philip A Klenotic Meng Cui Meinan Lyu Christopher E Morgan Edward W Yu Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.
description	The mycobacterial membrane protein large 3 (MmpL3) transporter is essential and required for shuttling the lipid trehalose monomycolate (TMM), a precursor of mycolic acid (MA)-containing trehalose dimycolate (TDM) and mycolyl arabinogalactan peptidoglycan (mAGP), in Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium smegmatis. However, the mechanism that MmpL3 uses to facilitate the transport of fatty acids and lipidic elements to the mycobacterial cell wall remains elusive. Here, we report 7 structures of the M. smegmatis MmpL3 transporter in its unbound state and in complex with trehalose 6-decanoate (T6D) or TMM using single-particle cryo-electron microscopy (cryo-EM) and X-ray crystallography. Combined with calculated results from molecular dynamics (MD) and target MD simulations, we reveal a lipid transport mechanism that involves a coupled movement of the periplasmic domain and transmembrane helices of the MmpL3 transporter that facilitates the shuttling of lipids to the mycobacterial cell wall.
format	article
author	Chih-Chia Su Philip A Klenotic Meng Cui Meinan Lyu Christopher E Morgan Edward W Yu
author_facet	Chih-Chia Su Philip A Klenotic Meng Cui Meinan Lyu Christopher E Morgan Edward W Yu
author_sort	Chih-Chia Su
title	Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.
title_short	Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.
title_full	Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.
title_fullStr	Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.
title_full_unstemmed	Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.
title_sort	structures of the mycobacterial membrane protein mmpl3 reveal its mechanism of lipid transport.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c854280c53b8409988242410fd435240
work_keys_str_mv	AT chihchiasu structuresofthemycobacterialmembraneproteinmmpl3revealitsmechanismoflipidtransport AT philipaklenotic structuresofthemycobacterialmembraneproteinmmpl3revealitsmechanismoflipidtransport AT mengcui structuresofthemycobacterialmembraneproteinmmpl3revealitsmechanismoflipidtransport AT meinanlyu structuresofthemycobacterialmembraneproteinmmpl3revealitsmechanismoflipidtransport AT christopheremorgan structuresofthemycobacterialmembraneproteinmmpl3revealitsmechanismoflipidtransport AT edwardwyu structuresofthemycobacterialmembraneproteinmmpl3revealitsmechanismoflipidtransport
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Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.

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