Structural elucidation of the hexameric MmpS4-MmpL4 complex from <i>Mycobacterium tuberculosis</i>.

ABSTRACT: Mycobacterium tuberculosis contains thirteen Mycobacterial membrane protein Large (MmpL) transporters, which belong to the family of secondary active RND transporters. MmpL4 and MmpL5, together with their operon partners MmpS4 and MmpS5, export the mycobacterial siderophore mycobactin and the last resort TB drug bedaquiline. Recently, we determined a structure of the MmpL4 monomer in complex with desferrated mycobactin, which lacked a functionally essential coiled-coil domain predicted to extend far into the periplasm. Here, we present a cryo-EM structure of the hexameric (MmpS4)₃-(MmpL4)₃ complex, which was enabled by rational disulfide cross-links based on AlphaFold predictions. We observed density for the coiled-coil domain, which protrudes into the periplas

SUBMITTER: Earp JC 

PROVIDER: S-EPMC12803245 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature