7K8C

CryoEM structure of a trehalose monomycolate transporter in lipid nanodiscs

Summary for 7K8C

• Entry DOI: 10.2210/pdb7k8c/pdb
• EMDB information: 22724 22726
• Descriptor: Trehalose monomycolate exporter MmpL3 (1 entity in total)
• Functional Keywords: trehalose monomycolate transporter, translocase
• Biological source: Mycolicibacterium smegmatis (Mycobacterium smegmatis)
• Total number of polymer chains: 1
• Total formula weight: 109509.22

Authors

Su, C.-C. (deposition date: 2020-09-26, release date: 2021-09-22, Last modification date: 2024-05-29)

Primary citation

Su, C.C.,Klenotic, P.A.,Cui, M.,Lyu, M.,Morgan, C.E.,Yu, E.W.
Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.
Plos Biol., 19:e3001370-e3001370, 2021

PubMed 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.

PubMed: 34383749
DOI: 10.1371/journal.pbio.3001370

Experimental method

ELECTRON MICROSCOPY (4.27 Å)