8POO

Low resolution structure of inactive conformation of the Ktr cation channel in presence of ATP and c-di-AMP

8POO の概要

• エントリーDOI: 10.2210/pdb8poo/pdb
• 分子名称: Ktr system potassium uptake protein B, Ktr system potassium uptake protein A (2 entities in total)
• 機能のキーワード: ktr channel, membrane protein
• 由来する生物種: Bacillus subtilis subsp. subtilis str. 168; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 322041.02

構造登録者

Cereija, T.B.,Teixeira-Duarte, C.M.,Morais-Cabral, J.H. (登録日: 2023-07-05, 公開日: 2024-05-15)

主引用文献

Rocha, R.,Jorge, J.M.P.,Teixeira-Duarte, C.M.,Figueiredo-Costa, I.R.,Cereija, T.B.,Ferreira-Teixeira, P.F.,Herzberg, C.,Stulke, J.,Morais-Cabral, J.H.
c-di-AMP determines the hierarchical organization of bacterial RCK proteins.
Proc.Natl.Acad.Sci.USA, 121:e2318666121-e2318666121, 2024

PubMed Abstract: In bacteria, intracellular K is involved in the regulation of membrane potential, cytosolic pH, and cell turgor as well as in spore germination, environmental adaptation, cell-to-cell communication in biofilms, antibiotic sensitivity, and infectivity. The second messenger cyclic-di-AMP (c-di-AMP) has a central role in modulating the intracellular K concentration in many bacterial species, controlling transcription and function of K channels and transporters. However, our understanding of how this regulatory network responds to c-di-AMP remains poor. We used the RCK (Regulator of Conductance of K) proteins that control the activity of Ktr channels in as a model system to analyze the regulatory function of c-di-AMP with a combination of in vivo and in vitro functional and structural characterization. We determined that the two RCK proteins (KtrA and KtrC) are neither physiologically redundant or functionally equivalent. KtrC is the physiologically dominant RCK protein in the regulation of Ktr channel activity. In explaining this hierarchical organization, we found that, unlike KtrA, KtrC is very sensitive to c-di-AMP inactivation and lack of c-di-AMP regulation results in RCK protein toxicity, most likely due to unregulated K flux. We also found that KtrC can assemble with KtrA, conferring c-di-AMP regulation to the functional KtrA/KtrC heteromers and potentially compensating KtrA toxicity. Altogether, we propose that the central role of c-di-AMP in the control of the K machinery, by modulating protein levels through gene transcription and by regulating protein activity, has determined the evolutionary selection of KtrC as the dominant RCK protein, shaping the hierarchical organization of regulatory components of the K machinery.

PubMed: 38652747
DOI: 10.1073/pnas.2318666121

実験手法

X-RAY DIFFRACTION (5.77 Å)