{"id":14714,"date":"2024-06-26T09:02:10","date_gmt":"2024-06-26T09:02:10","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=14714"},"modified":"2024-06-26T09:02:10","modified_gmt":"2024-06-26T09:02:10","slug":"2024-structure-and-mechanism-of-the-k-h-exchanger-kefc","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2024-structure-and-mechanism-of-the-k-h-exchanger-kefc\/","title":{"rendered":"2024 &#8211; Structure and mechanism of the K+\/H+ exchanger KefC"},"content":{"rendered":"<p>Intracellular potassium (K<sup>+<\/sup>) homeostasis is fundamental to cell viability. In addition to channels, K<sup>+<\/sup>\u00a0levels are maintained by various ion transporters. One major family is the proton-driven K<sup>+<\/sup>\u00a0efflux transporters, which in gram-negative bacteria is important for detoxification and in plants is critical for efficient photosynthesis and growth. Despite their importance, the structure and molecular basis for K<sup>+<\/sup>-selectivity is poorly understood. Here, we report ~3.1\u2009\u00c5 resolution cryo-EM structures of the\u00a0<i>Escherichia coli<\/i>\u00a0glutathione (GSH)-gated K<sup>+<\/sup>\u00a0efflux transporter KefC in complex with AMP, AMP\/GSH and an ion-binding variant. KefC forms a homodimer similar to the inward-facing conformation of Na<sup>+<\/sup>\/H<sup>+<\/sup>\u00a0antiporter NapA. By structural assignment of a coordinated K<sup>+<\/sup>\u00a0ion, MD simulations, and SSM-based electrophysiology, we demonstrate how ion-binding in KefC is adapted for binding a dehydrated K<sup>+<\/sup>\u00a0ion. KefC harbors C-terminal regulator of K<sup>+<\/sup>\u00a0conductance (RCK) domains, as present in some bacterial K<sup>+<\/sup>-ion channels. The domain-swapped helices in the RCK domains bind AMP and GSH and they inhibit transport by directly interacting with the ion-transporter module. Taken together, we propose that KefC is activated by detachment of the RCK domains and that ion selectivity exploits the biophysical properties likewise adapted by K<sup>+<\/sup>-ion-channels.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[36],"resource_type":[75],"application_areas":[53,108],"therapeutic_areas":[143],"target_categories":[60],"target_families":[349],"targets":[486],"resource_keyword":[],"class_list":["post-14714","resource_library","type-resource_library","status-publish","hentry","products_tags-surfe2r-n1","resource_type-publication","application_areas-assay-development-and-validation","application_areas-transporters","therapeutic_areas-assay-development-and-validation","target_categories-transporters","target_families-prokaryotic-pores","targets-glutathione-gsh-gated-k-efflux-transporter-kefc"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/14714","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=14714"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=14714"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=14714"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=14714"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=14714"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=14714"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=14714"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=14714"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=14714"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}