7n6b
From Proteopedia
Structure of MmpL3 reconstituted into lipid nanodisc in the TMM bound state
Structural highlights
FunctionMMPL3_MYCS2 Transports trehalose monomycolate (TMM) to the cell wall (PubMed:22520756, PubMed:28698380, PubMed:31239378). Flips TMM across the inner membrane. Membrane potential is not required for this function (PubMed:28698380). Transports probably phosphatidylethanolamine (PE) as well. Binds specifically both TMM and PE, but not trehalose dimycolate (TDM). Binds also diacylglycerol (DAG) and other phospholipids, including phosphatidylglycerol (PG), phosphatidylinositol (PI), and cardiolipin (CDL) (PubMed:31113875). Contributes to membrane potential, cell wall composition, antibiotic susceptibility and fitness (PubMed:28703701).[1] [2] [3] [4] [5] Publication Abstract from PubMedThe 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. Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.,Su CC, Klenotic PA, Cui M, Lyu M, Morgan CE, Yu EW PLoS Biol. 2021 Aug 12;19(8):e3001370. doi: 10.1371/journal.pbio.3001370., eCollection 2021 Aug. PMID:34383749[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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