A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB

Abstract K+ homeostasis is crucial for bacterial survival. The bacterial K+ channel KtrAB is regulated by the binding of ADP and ATP to the cytosolic RCK subunits KtrA. While the ligand-induced conformational changes in KtrA are well described, the transmission to the gating regions within KtrB is n...

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Main Authors: Janina Stautz, David Griwatz, Susann Kaltwasser, Ahmad Reza Mehdipour, Sophie Ketter, Celina Thiel, Dorith Wunnicke, Marina Schrecker, Deryck J. Mills, Gerhard Hummer, Janet Vonck, Inga Hänelt
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59546-z
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Summary:Abstract K+ homeostasis is crucial for bacterial survival. The bacterial K+ channel KtrAB is regulated by the binding of ADP and ATP to the cytosolic RCK subunits KtrA. While the ligand-induced conformational changes in KtrA are well described, the transmission to the gating regions within KtrB is not understood. Here, we present a cryo-EM structure of the ADP-bound, inactive KtrAB complex from Vibrio alginolyticus, which resolves part of KtrB’s N termini. They are short intrinsically disordered regions (IDRs) located at the interface of KtrA and KtrB. We reveal that these IDRs play a decisive role in ATP-mediated channel opening, while the closed ADP-bound state does not depend on the N-termini. We propose an allosteric mechanism, in which ATP-induced conformational changes within KtrA trigger an interaction of KtrB’s N-terminal IDRs with the membrane, stabilizing the active and conductive state of KtrAB.
ISSN:2041-1723