1. Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.
- Author
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Su CC, Klenotic PA, Cui M, Lyu M, Morgan CE, and Yu EW
- Subjects
- Bacterial Proteins ultrastructure, Cryoelectron Microscopy, Decanoates metabolism, Escherichia coli, Membrane Transport Proteins ultrastructure, Molecular Dynamics Simulation, Mycobacterium smegmatis ultrastructure, Trehalose metabolism, Bacterial Proteins metabolism, Cord Factors metabolism, Lipid Metabolism, Membrane Transport Proteins metabolism, Mycobacterium smegmatis metabolism
- 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., Competing Interests: The authors have declared that no competing interests exist. more...
- Published
- 2021
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