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

被引：3

作者：

Chiang, Wesley Tien ^{[1
]}

Chang, Yao-Kai ^{[2
]}

Hui, Wei-Han ^{[3
]}

Chang, Shu-Wei ^{[3
,4
]}

Liao, Chen-Yi ^{[1
]}

Chang, Yi-Chuan ^{[1
]}

Chen, Chun-Jung ^{[5
]}

Wang, Wei-Chen ^{[6
]}

Lai, Chien-Chen ^{[6
,7
]}

Wang, Chun-Hsiung ^{[2
]}

Luo, Siou-Ying ^{[2
]}

Huang, Ya-Ping ^{[2
]}

Chou, Shan-Ho ^{[1
]}

Horng, Tzyy-Leng ^{[8
]}

Hou, Ming-Hon ^{[9
]}

Muench, Stephen P. ^{[10
,11
]}

Chen, Ren-Shiang ^{[12
]}

Tsai, Ming-Daw ^{[2
,13
]}

Hu, Nien-Jen ^{[1
,14
]}

机构：

[1] Natl Chung Hsing Univ, Grad Inst Biotechnol, Taichung 402202, Taiwan

[2] Acad Sinica, Inst Biol Chem, Taipei 115201, Taiwan

[3] Natl Taiwan Univ, Dept Civil Engn, Taipei City 106319, Taiwan

[4] Natl Taiwan Univ, Dept Biomed Engn, Taipei 10663, Taiwan

[5] Natl Synchrotron Radiat Res Ctr, Sci Res Div, Life Sci Grp, Hsinchu 30092, Taiwan

[6] Natl Chung Hsing Univ, Inst Mol Biol, Taichung 402202, Taiwan

[7] China Med Univ, Grad Inst Chinese Med Sci, Taichung 406040, Taiwan

[8] Feng Chia Univ, Dept Appl Math, Taichung 407102, Taiwan

[9] Natl Chung Hsing Univ, Inst Genom & Bioinformat, Taichung 402202, Taiwan

[10] Univ Leeds, Fac Biol Sci, Sch Biomed Sci, Leeds LS2 9JT, England

[11] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, England

[12] Tunghai Univ, Dept Life Sci, Taichung 407224, Taiwan

[13] Natl Taiwan Univ, Inst Biochem Sci, Taipei 106319, Taiwan

[14] Natl Chung Hsing Univ, Ph D Program Translat Med, Taichung 402202, Taiwan

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

MEMBRANE REGION M-2C2; VIBRIO-ALGINOLYTICUS; POTASSIUM CHANNEL; GATING RING; RCK DOMAIN; PROTEIN; SODIUM; TRANSPORT; BINDING; SLO2.2;

D O I：

10.1038/s41467-024-48057-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 & Aring;. 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.

引用

页数：14

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