In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 8 ( 2021-8-12), p. e3001370-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001370
DOI:
10.1371/journal.pbio.3001370.g001
DOI:
10.1371/journal.pbio.3001370.g002
DOI:
10.1371/journal.pbio.3001370.g003
DOI:
10.1371/journal.pbio.3001370.g004
DOI:
10.1371/journal.pbio.3001370.g005
DOI:
10.1371/journal.pbio.3001370.g006
DOI:
10.1371/journal.pbio.3001370.g007
DOI:
10.1371/journal.pbio.3001370.g008
DOI:
10.1371/journal.pbio.3001370.s001
DOI:
10.1371/journal.pbio.3001370.s002
DOI:
10.1371/journal.pbio.3001370.s003
DOI:
10.1371/journal.pbio.3001370.s004
DOI:
10.1371/journal.pbio.3001370.s005
DOI:
10.1371/journal.pbio.3001370.s006
DOI:
10.1371/journal.pbio.3001370.s007
DOI:
10.1371/journal.pbio.3001370.s008
DOI:
10.1371/journal.pbio.3001370.s009
DOI:
10.1371/journal.pbio.3001370.s010
DOI:
10.1371/journal.pbio.3001370.s011
DOI:
10.1371/journal.pbio.3001370.s012
DOI:
10.1371/journal.pbio.3001370.s013
DOI:
10.1371/journal.pbio.3001370.s014
DOI:
10.1371/journal.pbio.3001370.r001
DOI:
10.1371/journal.pbio.3001370.r002
DOI:
10.1371/journal.pbio.3001370.r003
DOI:
10.1371/journal.pbio.3001370.r004
DOI:
10.1371/journal.pbio.3001370.r005
DOI:
10.1371/journal.pbio.3001370.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X
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