8WCW

Cryo-EM structure of MsRv1273c/72c from Mycobacterium smegmatis in the IFapo state

8WCW の概要

• エントリーDOI: 10.2210/pdb8wcw/pdb
• EMDBエントリー: 37450
• 分子名称: Transmembrane ATP-binding protein ABC transporter, ABC transporter transmembrane region (2 entities in total)
• 機能のキーワード: abc transporter, exporter, transport protein
• 由来する生物種: Mycolicibacterium smegmatis MC2 155; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 133320.77

構造登録者

Yu, J.,Li, J. (登録日: 2023-09-14, 公開日: 2025-03-26, 最終更新日: 2025-05-14)

主引用文献

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

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: 40295516
DOI: 10.1038/s41467-025-59300-5

実験手法

ELECTRON MICROSCOPY (3.11 Å)