9VKS

Cryo-EM structure of F-ATP synthase c-ring from Mycobacteroides abscessus (Backbone)

9VKS の概要

• エントリーDOI: 10.2210/pdb9vks/pdb
• EMDBエントリー: 65141
• 分子名称: ATP synthase subunit c (1 entity in total)
• 機能のキーワード: hydrolase, atp synthase, membrane protein, mycobacterium abscessus, mycobacterial, c-ring, nontuberculous mycobacteria
• 由来する生物種: Mycobacteroides abscessus subsp. abscessus
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 73426.28

構造登録者

Fong, T.C.,Saw, W.-G.,Mathiyazakan, V.,Wong, C.F.,Grueber, G. (登録日: 2025-06-23, 公開日: 2026-01-14, 最終更新日: 2026-03-25)

主引用文献

Fong, T.C.,Saw, W.G.,Mathiyazakan, V.,Wong, C.F.,Gruber, G.
The Mycobacterium abscessus F-ATP synthase structure reveals mechanistic elements enabling rational drug design to combat NTM lung disease.
Structure, 34:508-520.e3, 2026

PubMed Abstract: The increasing global incidence rate of nontuberculous mycobacteria pulmonary infections is an emerging public health crisis, with Mycobacterium abscessus (Mab) being one of the most virulent and treatment-refractory of these pathogens. Mab exhibits extensive intrinsic and acquired drug resistance mechanisms that neutralize most antimicrobials against this pathogen, causing a clinical conundrum. As Mab relies on oxidative phosphorylation as its main energy source, its essential F-ATP synthase is a promising drug target but remains poorly understood due to a lack of host expression systems. Here, we present the expression, isolation, and structural characterization of Mab's F-ATP synthase. Cryo-EM reveals three nucleotide-driven rotational states at atomic resolution, highlighting key catalytic centers, a mycobacteria-specific α-subunit extension involved in the inhibition of ATP hydrolysis, energy transmission via the γε-stalk, and mechanochemical coupling by the δ-subunit. The structural blueprint allows precise target engagement and optimization of hits-to-leads and existing anti-Mab inhibitors targeting the engine.

PubMed: 41475343
DOI: 10.1016/j.str.2025.12.005

実験手法

ELECTRON MICROSCOPY (5.61 Å)