Helical jackknives control the gates of the double-pore K+ uptake system KtrAB
Autor(en): | Diskowski, Marina Mehdipour, Ahmad Reza Wunnicke, Dorith Mills, Deryck J. Mikusevic, Vedrana Baerland, Natalie Hoffmann, Jan Morgner, Nina Steinhoff, Heinz-Juergen Hummer, Gerhard Vonck, Janet Haenelt, Inga |
Stichwörter: | BETAINE CARRIER BETP; Biology; CORYNEBACTERIUM-GLUTAMICUM; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ION-CHANNEL; Life Sciences & Biomedicine - Other Topics; MEMBRANE REGION M-2C2; MOLECULAR-DYNAMICS; POTASSIUM-TRANSPORT; SEQUENCE ALIGNMENT; VIBRIO-ALGINOLYTICUS | Erscheinungsdatum: | 2017 | Herausgeber: | ELIFE SCIENCES PUBLICATIONS LTD | Journal: | ELIFE | Volumen: | 6 | Zusammenfassung: | Ion channel gating is essential for cellular homeostasis and is tightly controlled. In some eukaryotic and most bacterial ligand-gated K+ channels, RCK domains regulate ion fluxes. Until now, a single regulatory mechanism has been proposed for all RCK-regulated channels, involving signal transduction from the RCK domain to the gating area. Here, we present an inactive ADP-bound structure of KtrAB from Vibrio alginolyticus, determined by cryo-electron microscopy, which, combined with EPR spectroscopy and molecular dynamics simulations, uncovers a novel regulatory mechanism for ligand-induced action at a distance. Exchange of activating ATP to inactivating ADP triggers short helical segments in the K+-translocating KtrB dimer to organize into two long helices that penetrate deeply into the regulatory RCK domains, thus connecting nucleotide-binding sites and ion gates. As KtrAB and its homolog TrkAH have been implicated as bacterial pathogenicity factors, the discovery of this functionally relevant inactive conformation may advance structure-guided drug development. |
ISSN: | 2050084X | DOI: | 10.7554/eLife.24303 |
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geprüft am 17.05.2024