8B70

KimA from B. subtilis with nucleotide second-messenger c-di-AMP bound

8B70 の概要

• エントリーDOI: 10.2210/pdb8b70/pdb
• EMDBエントリー: 15894
• 分子名称: Potassium transporter KimA, (2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-2,9-bis(6-amino-9H-purin-9-yl)octahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8 ]tetraoxadiphosphacyclododecine-3,5,10,12-tetrol 5,12-dioxide, DODECYL-BETA-D-MALTOSIDE, ... (4 entities in total)
• 機能のキーワード: potassium importer, second-messenger, c-di-amp, membrane protein
• 由来する生物種: Bacillus subtilis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 138647.28

構造登録者

Vonck, J.,Wieferig, J.P. (登録日: 2022-09-28, 公開日: 2023-01-18, 最終更新日: 2024-07-24)

主引用文献

Fuss, M.F.,Wieferig, J.P.,Corey, R.A.,Hellmich, Y.,Tascon, I.,Sousa, J.S.,Stansfeld, P.J.,Vonck, J.,Hanelt, I.
Cyclic di-AMP traps proton-coupled K + transporters of the KUP family in an inward-occluded conformation.
Nat Commun, 14:3683-3683, 2023

PubMed Abstract: Cyclic di-AMP is the only known essential second messenger in bacteria and archaea, regulating different proteins indispensable for numerous physiological processes. In particular, it controls various potassium and osmolyte transporters involved in osmoregulation. In Bacillus subtilis, the K/H symporter KimA of the KUP family is inactivated by c-di-AMP. KimA sustains survival at potassium limitation at low external pH by mediating potassium ion uptake. However, at elevated intracellular K concentrations, further K accumulation would be toxic. In this study, we reveal the molecular basis of how c-di-AMP binding inhibits KimA. We report cryo-EM structures of KimA with bound c-di-AMP in detergent solution and reconstituted in amphipols. By combining structural data with functional assays and molecular dynamics simulations we reveal how c-di-AMP modulates transport. We show that an intracellular loop in the transmembrane domain interacts with c-di-AMP bound to the adjacent cytosolic domain. This reduces the mobility of transmembrane helices at the cytosolic side of the K binding site and therefore traps KimA in an inward-occluded conformation.

PubMed: 37344476
DOI: 10.1038/s41467-023-38944-1

実験手法

ELECTRON MICROSCOPY (3.3 Å)