{"id":6393,"date":"2023-02-17T07:07:14","date_gmt":"2023-02-17T07:07:14","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2020-conformational-equilibrium-shift-underlies-altered-k-channel-gating-as-revealed-by-nmr\/"},"modified":"2023-02-17T07:07:15","modified_gmt":"2023-02-17T07:07:15","slug":"2020-conformational-equilibrium-shift-underlies-altered-k-channel-gating-as-revealed-by-nmr","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2020-conformational-equilibrium-shift-underlies-altered-k-channel-gating-as-revealed-by-nmr\/","title":{"rendered":"2020 &#8211; Conformational equilibrium shift underlies altered K<sup>+<\/sup> channel gating as revealed by NMR"},"content":{"rendered":"<p>The potassium ion (K<sup>+<\/sup>) channel plays a fundamental role in controlling K<sup>+<\/sup>\u00a0permeation across the cell membrane and regulating cellular excitabilities. Mutations in the transmembrane pore reportedly affect the gating transitions of K<sup>+<\/sup>\u00a0channels, and are associated with the onset of neural disorders. However, due to the lack of structural and dynamic insights into the functions of K<sup>+<\/sup>\u00a0channels, the structural mechanism by which these mutations cause K<sup>+<\/sup>\u00a0channel dysfunctions remains elusive. Here, we used nuclear magnetic resonance spectroscopy to investigate the structural mechanism underlying the decreased K<sup>+<\/sup>-permeation caused by disease-related mutations, using the prokaryotic K<sup>+<\/sup>\u00a0channel KcsA. We demonstrated that the conformational equilibrium in the transmembrane region is shifted toward the non-conductive state with the closed intracellular K<sup>+<\/sup>-gate in the disease-related mutant. We also demonstrated that this equilibrium shift is attributable to the additional steric contacts in the open-conductive structure, which are evoked by the increased side-chain bulkiness of the residues lining the transmembrane helix. Our results suggest that the alteration in the conformational equilibrium of the intracellular K<sup>+<\/sup>-gate is one of the fundamental mechanisms underlying the dysfunctions of K<sup>+<\/sup>\u00a0channels caused by disease-related mutations.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45,129],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[],"target_categories":[61],"target_families":[350],"targets":[130],"resource_keyword":[],"class_list":["post-6393","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","products_tags-vesicle-prep-pro","resource_type-publication","application_areas-ion-channels","target_categories-voltage-gated-ion-channels","target_families-prokaryotic-tetrameric-cation-channels","targets-ph-gated-potassium-channel-kcsa"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6393","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6393"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6393"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6393"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6393"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6393"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6393"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6393"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6393"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6393"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}