9OJN

Structure of Mycobacterium smegmatis EtfD

This is a non-PDB format compatible entry.

Summary for 9OJN

• Entry DOI: 10.2210/pdb9ojn/pdb
• EMDB information: 70545
• Descriptor: Iron-sulfur-binding reductase, DODECYL-BETA-D-MALTOSIDE, MENAQUINONE-9, ... (7 entities in total)
• Functional Keywords: oxidoreductase, membrane protein, electron transport chain, beta oxidation
• Biological source: Mycolicibacterium smegmatis MC2 155
• Total number of polymer chains: 1
• Total formula weight: 114308.67

Authors

Courbon, G.M.,Rubinstein, J.L. (deposition date: 2025-05-08, release date: 2025-05-21, Last modification date: 2026-04-29)

Primary citation

Courbon, G.M.,Makarov, V.,Cole, S.T.,Schnapinger, D.,Ehrt, S.,Rubinstein, J.L.
Structural basis for EtfD-mediated coupling of beta-oxidation and the respiratory chain in mycobacteria.
Embo J., 45:2785-2807, 2026

PubMed Abstract: Targeting β-oxidation has been proposed as a strategy for shortening tuberculosis (TB) treatment by killing non-replicating Mycobacterium tuberculosis within granulomas where the pathogen relies on host-derived lipids. The protein EtfD is thought to couple β-oxidation of fatty acids with the respiratory chain in mycobacteria. However, the structure of EtfD is not known and, as the presumed link between two complex processes, its activity has been difficult to measure, impeding its exploitation as a drug target. Here we show that Mycobacterium smegmatis, a fast growing and nonpathogenic model for M. tuberculosis, relies on EtfD for extracting energy from β-oxidation. The electron cryomicroscopy structure of M. smegmatis EtfD reveals an unusual linear [3Fe-4S] cluster that has not been seen in other protein structures, and suggests how EtfD transfers electrons from β-oxidation to the respiratory chain. We devised an assay that couples EtfD activity to a fluorescent readout of proton pumping by the respiratory chain, which can be used to identify compounds that block mycobacteria from using β-oxidation to power oxidative phosphorylation.

PubMed: 41844842
DOI: 10.1038/s44318-026-00726-y

Experimental method

ELECTRON MICROSCOPY (3.2 Å)