9IQG
Cryo-EM structure of MsRv1273c/72c from Mycobacterium smegmatis in the ATP|ADP+Vi-bound Occ (Vi) state
Summary for 9IQG
| Entry DOI | 10.2210/pdb9iqg/pdb |
| EMDB information | 60791 |
| Descriptor | ABC transporter, ATP-binding protein, ABC transporter transmembrane region, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total) |
| Functional Keywords | abc transporter, exporter, transport protein |
| Biological source | Mycolicibacterium smegmatis MC2 155 More |
| Total number of polymer chains | 2 |
| Total formula weight | 135031.43 |
| Authors | |
| Primary citation | Yu, J.,Lan, Y.,Zhu, C.,Chen, Z.,Pan, J.,Shi, Y.,Yang, L.,Hu, T.,Gao, Y.,Zhao, Y.,Chen, X.,Yang, X.,Lu, S.,Guddat, L.W.,Yang, H.,Rao, Z.,Li, J. Structure and mechanism of a mycobacterial isoniazid efflux pump MsRv1273c/72c with a degenerate nucleotide-binding site. Nat Commun, 16:3969-3969, 2025 Cited by PubMed 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 the function of both NBSs through conformational changes. Thus, these data provide insights into the mechanism of this heterodimeric ABC transporter containing a degenerate NBS. The structures also provide a framework for the rational design of anti-tuberculosis drugs targeting this drug-efflux pump. PubMed: 40295516DOI: 10.1038/s41467-025-59300-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.7 Å) |
Structure validation
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