Structure and mechanism of a mycobacterial isoniazid efflux pump MsRv1273c/72c with a degenerate nucleotide-binding site.

ABSTRACT: Heterodimeric ATP-binding cassette (ABC) transporters containing one catalytically impaired degenerate nucleotide-binding site (NBS) have a mechanism different from those with two active NBSs. However, the structural basis of their transport mechanism remains to be explained. Here, we determine mycobacterial MsRv1273c/72c to be an isoniazid efflux pump and determine several structures by cryo-electron microscopy showing specific asymmetrical features including an N-terminal extending loop and a periplasmic helical hairpin only found in MsRv1272c. In addition, we capture three distinct asymmetric states where the nucleotide-binding domains are partially dimerized at the degenerate site. Using these intermediate states, the D-WalkerB loop and X-signature loop of MsRv1272c modulate and couple

SUBMITTER: Yu J 

PROVIDER: S-EPMC12038006 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature