Structural basis and synergism of ATP and Na + activation in bacterial K + uptake system KtrAB.

Autor: Chiang WT; Graduate Institute of Biochemistry, National Chung Hsing University, Taichung, 402202, Taiwan., Chang YK; Institute of Biological Chemistry, Academia Sinica, Taipei, 115201, Taiwan., Hui WH; Department of Civil Engineering, National Taiwan University, Taipei, 106319, Taiwan., Chang SW; Department of Civil Engineering, National Taiwan University, Taipei, 106319, Taiwan.; Department of Biomedical Engineering, National Taiwan University, Taipei, 10663, Taiwan., Liao CY; Graduate Institute of Biochemistry, National Chung Hsing University, Taichung, 402202, Taiwan., Chang YC; Graduate Institute of Biochemistry, National Chung Hsing University, Taichung, 402202, Taiwan., Chen CJ; Life Science Group, Scientific Research Division, National Synchrotron Radiation Research Center, Hsinchu, 30092, Taiwan., Wang WC; Institute of Molecular Biology, National Chung Hsing University, Taichung, 402202, Taiwan., Lai CC; Institute of Molecular Biology, National Chung Hsing University, Taichung, 402202, Taiwan.; Graduate Institute of Chinese Medical Science, China Medical University, Taichung, 406040, Taiwan., Wang CH; Institute of Biological Chemistry, Academia Sinica, Taipei, 115201, Taiwan., Luo SY; Institute of Biological Chemistry, Academia Sinica, Taipei, 115201, Taiwan., Huang YP; Institute of Biological Chemistry, Academia Sinica, Taipei, 115201, Taiwan., Chou SH; Graduate Institute of Biochemistry, National Chung Hsing University, Taichung, 402202, Taiwan., Horng TL; Department of Applied Mathematics, Feng Chia University, Taichung, 407102, Taiwan., Hou MH; Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, 402202, Taiwan., Muench SP; School of Biomedical Sciences, Faculty of Biological Sciences and the Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Chen RS; Department of Life Science, Tunghai University, Taichung, 407224, Taiwan., Tsai MD; Institute of Biological Chemistry, Academia Sinica, Taipei, 115201, Taiwan. mdtsai@gate.sinica.edu.tw.; Institute of Biochemical Sciences, National Taiwan University, Taipei, 106319, Taiwan. mdtsai@gate.sinica.edu.tw., Hu NJ; Graduate Institute of Biochemistry, National Chung Hsing University, Taichung, 402202, Taiwan. njhu@nchu.edu.tw.; Ph.D Program in Translational Medicine, National Chung Hsing University, Taichung, 402202, Taiwan. njhu@nchu.edu.tw.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 08; Vol. 15 (1), pp. 3850. Date of Electronic Publication: 2024 May 08.
DOI: 10.1038/s41467-024-48057-y
Abstrakt: The K + uptake system KtrAB is essential for bacterial survival in low K + environments. The activity of KtrAB is regulated by nucleotides and Na + . Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na + activates KtrAB and the Na + binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na + , as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na + binding stabilizes the ATP-bound BsKtrAB complex and enhances its K + flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na + in activating BsKtrAB is likely applicable to Na + -activated K + channels in central nervous system.
(© 2024. The Author(s).)
Databáze: MEDLINE
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