{"id":16434,"date":"2024-11-05T15:15:18","date_gmt":"2024-11-05T15:15:18","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=16434"},"modified":"2024-11-05T15:15:18","modified_gmt":"2024-11-05T15:15:18","slug":"2024-lychos-is-a-human-hybrid-of-a-plant-like-pin-transporter-and-a-gpcr","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2024-lychos-is-a-human-hybrid-of-a-plant-like-pin-transporter-and-a-gpcr\/","title":{"rendered":"2024 &#8211; LYCHOS is a human hybrid of a plant-like PIN transporter and a GPCR"},"content":{"rendered":"<p>Lysosomes have crucial roles in regulating eukaryotic metabolism and cell growth by acting as signalling platforms to sense and respond to changes in nutrient and energy availability<sup><a id=\"ref-link-section-d131457265e577\" title=\"Settembre, C. &amp; Perera, R. M. Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology. Nat. Rev. Mol. Cell Biol. 25, 223\u2013245 (2024).\" href=\"https:\/\/www.nature.com\/articles\/s41586-024-08012-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a><\/sup>. LYCHOS (GPR155) is a lysosomal transmembrane protein that functions as a cholesterol sensor, facilitating the cholesterol-dependent activation of the master protein kinase mechanistic target of rapamycin complex\u20091 (mTORC1)<sup><a id=\"ref-link-section-d131457265e581\" title=\"Shin, H. R. et al. Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1. Science 377, 1290\u20131298 (2022).\" href=\"https:\/\/www.nature.com\/articles\/s41586-024-08012-9#ref-CR2\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\">2<\/a><\/sup>. However, the structural basis of LYCHOS assembly and activity remains unclear. Here we determine several high-resolution cryo-electron microscopy structures of human LYCHOS, revealing a homodimeric transmembrane assembly of a transporter-like domain fused to a G-protein-coupled receptor (GPCR) domain. The class B2-like GPCR domain is captured in the apo state and packs against the surface of the transporter-like domain, providing an unusual example of a GPCR as a domain in a larger transmembrane assembly. Cholesterol sensing is mediated by a conserved cholesterol-binding motif, positioned between the GPCR and transporter domains. We reveal that the LYCHOS transporter-like domain is an orthologue of the plant PIN-FORMED (PIN) auxin transporter family, and has greater structural similarity to plant auxin transporters than to known human transporters. Activity assays support a model in which the LYCHOS transporter and GPCR domains coordinate to sense cholesterol and regulate mTORC1 activation.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[36],"resource_type":[75],"application_areas":[53,76,108],"therapeutic_areas":[143,403],"target_categories":[60],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-16434","resource_library","type-resource_library","status-publish","hentry","products_tags-surfe2r-n1","resource_type-publication","application_areas-assay-development-and-validation","application_areas-drug-discovery","application_areas-transporters","therapeutic_areas-assay-development-and-validation","therapeutic_areas-lysosomal-diseases","target_categories-transporters"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/16434","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=16434"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=16434"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=16434"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=16434"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=16434"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=16434"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=16434"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=16434"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=16434"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}