3l9x

From Proteopedia

KefC C-terminal domain in complex with KefF and ESG

PDB ID 3l9x

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Structural highlights

3l9x is a 2 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KEFC_ECOLI Transport system that facilitates potassium-efflux, possibly by potassium-proton antiport.KEFF_ECOLI Regulatory subunit of a potassium efflux system that confers protection against electrophiles. Required for full activity of KefC. Shows redox enzymatic activity, but this enzymatic activity is not required for activation of KefC. Can use a wide range of substrates, including electrophilic quinones, and its function could be to reduce the redox toxicity of electrophilic quinones in parallel with acting as triggers for the KefC efflux system.[HAMAP-Rule:MF_01414]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Gram negative pathogens are protected against toxic electrophilic compounds by glutathione-gated potassium efflux systems (Kef) that modulate cytoplasmic pH. We have elucidated the mechanism of gating through structural and functional analysis of Escherichia coli KefC. The revealed mechanism can explain how subtle chemical differences in glutathione derivatives can produce opposite effects on channel function. Kef channels are regulated by potassium transport and NAD-binding (KTN) domains that sense both reduced glutathione, which inhibits Kef activity, and glutathione adducts that form during electrophile detoxification and activate Kef. We find that reduced glutathione stabilizes an interdomain association between two KTN folds, whereas large adducts sterically disrupt this interaction. F441 is identified as the pivotal residue discriminating between reduced glutathione and its conjugates. We demonstrate a major structural change on the binding of an activating ligand to a KTN-domain protein. Analysis of the regulatory interactions suggests strategies to disrupt pathogen potassium and pH homeostasis.

Mechanism of ligand-gated potassium efflux in bacterial pathogens.,Roosild TP, Castronovo S, Healy J, Miller S, Pliotas C, Rasmussen T, Bartlett W, Conway SJ, Booth IR Proc Natl Acad Sci U S A. 2010 Nov 1. PMID:21041667^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Miller S, Ness LS, Wood CM, Fox BC, Booth IR. Identification of an ancillary protein, YabF, required for activity of the KefC glutathione-gated potassium efflux system in Escherichia coli. J Bacteriol. 2000 Nov;182(22):6536-40. PMID:11053405 doi:10.1128/JB.182.22.6536-6540.2000
↑ Roosild TP, Castronovo S, Miller S, Li C, Rasmussen T, Bartlett W, Gunasekera B, Choe S, Booth IR. KTN (RCK) domains regulate K+ channels and transporters by controlling the dimer-hinge conformation. Structure. 2009 Jun 10;17(6):893-903. PMID:19523906 doi:10.1016/j.str.2009.03.018
↑ Lyngberg L, Healy J, Bartlett W, Miller S, Conway SJ, Booth IR, Rasmussen T. KefF, the regulatory subunit of the potassium efflux system KefC, shows quinone oxidoreductase activity. J Bacteriol. 2011 Sep;193(18):4925-32. PMID:21742892 doi:10.1128/JB.05272-11
↑ Roosild TP, Castronovo S, Healy J, Miller S, Pliotas C, Rasmussen T, Bartlett W, Conway SJ, Booth IR. Mechanism of ligand-gated potassium efflux in bacterial pathogens. Proc Natl Acad Sci U S A. 2010 Nov 1. PMID:21041667 doi:10.1073/pnas.1012716107