{"id":6158,"date":"2023-02-17T07:06:39","date_gmt":"2023-02-17T07:06:39","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2016-pore-architecture-of-tric-channels-and-insights-into-their-gating-mechanism\/"},"modified":"2023-02-17T07:06:40","modified_gmt":"2023-02-17T07:06:40","slug":"2016-pore-architecture-of-tric-channels-and-insights-into-their-gating-mechanism","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2016-pore-architecture-of-tric-channels-and-insights-into-their-gating-mechanism\/","title":{"rendered":"2016 &#8211; Pore architecture of TRIC channels and insights into their gating mechanism"},"content":{"rendered":"<p>Intracellular Ca<sup>2+<\/sup>\u00a0signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis. Release of Ca<sup>2+<\/sup>\u00a0from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR\/ER). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca<sup>2+<\/sup>\u00a0through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR\/ER lumen. Genetic ablations or mutations of TRIC channels are associated with hypertension, heart disease, respiratory defects and brittle bone disease. Despite the pivotal function of TRIC channels in Ca<sup>2+<\/sup>\u00a0signalling, their pore architectures and gating mechanisms remain unknown. Here we present the structures of TRIC-B1 and TRIC-B2 channels from\u00a0Caenorhabditis elegans\u00a0in complex with endogenous phosphatidylinositol-4,5-biphosphate (PtdIns(4,5)P2, also known as PIP2) lipid molecules. The TRIC-B1\/B2 proteins and PIP2\u00a0assemble into a symmetrical homotrimeric complex. Each monomer contains an hourglass-shaped hydrophilic pore contained within a seven-transmembrane-helix domain. Structural and functional analyses unravel the central role of PIP2\u00a0in stabilizing the cytoplasmic gate of the ion permeation pathway and reveal a marked Ca<sup>2+<\/sup>-induced conformational change in a cytoplasmic loop above the gate. A mechanistic model has been proposed to account for the complex gating mechanism of TRIC channels.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45,129],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[],"target_categories":[335],"target_families":[336,373],"targets":[258,272,273],"resource_keyword":[],"class_list":["post-6158","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-intracellular-regulated-ion-channels","target_families-calcium-release-receptors","target_families-trimeric-intracellular-cation-channels","targets-ryrs","targets-tric-a-tric-b","targets-ip3-receptors-insp3r"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6158","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=6158"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6158"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6158"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6158"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6158"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6158"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6158"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6158"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6158"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}