Structure and assembly of the MmpL5/MmpS5 efflux transporter from Mycobacterium tuberculosis.

ABSTRACT: The MmpL5/MmpS5 efflux system in Mycobacterium tuberculosis plays crucial roles in extruding therapeutic drugs (e.g., bedaquiline), and exporting siderophores (i.e., (carboxy)mycobactins). However, the molecular basis underlying these processes remains unknown due to the lack of structural information. Here, we report the cryo-electron microscopy structures of Mycobacterium tuberculosis MmpL5/MmpS5 at resolutions ranging from 2.64 to 3.31 Å, revealing it to be a trimer. The core of this complex is formed by three MmpL5 subunits assembled in a unique shoulder-to-shoulder ring-like configuration, with each MmpS5 subunit positioned between the two adjacent MmpL5 subunits. A remarkable feature of this system is the extracellular stalk, which spans approximately 130 Å in length and is composed

SUBMITTER: Xiong Z 

PROVIDER: S-EPMC12122801 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature