{"id":"https://openalex.org/W7203757655","doi":"https://doi.org/10.24406/publica-9895","title":"Allosteric switching of Ca2+ permeability in the lysosomal ion channel TPC2 underpins biased agonist activation","display_name":"Allosteric switching of Ca2+ permeability in the lysosomal ion channel TPC2 underpins biased agonist activation","publication_year":2026,"publication_date":"2026-01-01","ids":{"openalex":"https://openalex.org/W7203757655","doi":"https://doi.org/10.24406/publica-9895"},"language":"en","primary_location":{"id":"doi:10.24406/publica-9895","doi":"https://doi.org/10.24406/publica-9895","is_oa":true,"landing_page_url":"https://doi.org/10.24406/publica-9895","pdf_url":null,"source":{"id":"https://openalex.org/S4306400318","display_name":"Fraunhofer-Publica (Fraunhofer-Gesellschaft)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4923324","host_organization_name":"Fraunhofer-Gesellschaft","host_organization_lineage":["https://openalex.org/I4923324"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Other"},"volume":null,"type":"other","indexed_in":["datacite"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.24406/publica-9895","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5113084980","display_name":"Qianru Mu","orcid":"https://orcid.org/0009-0003-6748-5831","observed_orcids":["https://orcid.org/0009-0003-6748-5831"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mu, Qianru","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034850441","display_name":"Ryo\ufffd Saito","orcid":"https://orcid.org/0000-0002-1927-8147","observed_orcids":["https://orcid.org/0000-0002-1927-8147"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Saito, Ryo","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5145973879","display_name":"Franceska Ozola","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ozola, Franceska","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066979120","display_name":"Dawid Ja\u015blan","orcid":"https://orcid.org/0000-0002-0685-7633","observed_orcids":["https://orcid.org/0000-0002-0685-7633"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ja\u015blan, Dawid","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5146030262","display_name":"Pak Nin Chu","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Chu, Pak Nin","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081802445","display_name":"Afroditi Maria Zaki","orcid":"https://orcid.org/0000-0003-0992-9732","observed_orcids":["https://orcid.org/0000-0003-0992-9732"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Zaki, Afroditi Maria","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039030628","display_name":"Marcos Rubio\u2010Alarc\u00f3n","orcid":"https://orcid.org/0000-0002-3005-2149","observed_orcids":["https://orcid.org/0000-0002-3005-2149"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rubio-Alarcon, Marcos","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5030282424","display_name":"Marco Keller","orcid":"https://orcid.org/0000-0003-4792-3980","observed_orcids":["https://orcid.org/0000-0003-4792-3980"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Keller, Marco","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5072477935","display_name":"Yu Yuan","orcid":"https://orcid.org/0000-0002-4620-0249","observed_orcids":["https://orcid.org/0000-0002-4620-0249"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yuan, Yu","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046216376","display_name":"Alan Greig","orcid":"https://orcid.org/0000-0003-1408-4746","observed_orcids":["https://orcid.org/0000-0003-1408-4746"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Greig, Alan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5007944603","display_name":"Virginia Sili\u00f3","orcid":"https://orcid.org/0000-0002-3169-336X","observed_orcids":["https://orcid.org/0000-0002-3169-336X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sili\u00f3, Virginia","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046572292","display_name":"Franz Bracher","orcid":"https://orcid.org/0000-0003-0009-8629","observed_orcids":["https://orcid.org/0000-0003-0009-8629"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Bracher, Franz","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034236085","display_name":"Philip Charles Biggin","orcid":"https://orcid.org/0000-0001-5100-8836","observed_orcids":["https://orcid.org/0000-0001-5100-8836"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Biggin, Philip Charles","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060173368","display_name":"Gabriela Cristina Brailoiu","orcid":"https://orcid.org/0000-0002-2512-6545","observed_orcids":["https://orcid.org/0000-0002-2512-6545"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Brailoiu, Gabriela Cristina","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085776987","display_name":"Eugen Brailoiu","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Br\u00e3iloiu, Eugen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047013622","display_name":"Jonathan S. Marchant","orcid":"https://orcid.org/0000-0001-6592-0877","observed_orcids":["https://orcid.org/0000-0001-6592-0877"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Marchant, Jonathan S.","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5018377011","display_name":"Christian M. Grimm","orcid":"https://orcid.org/0000-0002-0177-5559","observed_orcids":["https://orcid.org/0000-0002-0177-5559"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Grimm, Christian","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036306949","display_name":"Eric J. Lambie","orcid":"https://orcid.org/0000-0002-7371-128X","observed_orcids":["https://orcid.org/0000-0002-7371-128X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lambie, Eric J.","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5123377729","display_name":"Taufiq Rahman","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rahman, Taufiq","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5086481218","display_name":"Sandip Patel","orcid":"https://orcid.org/0000-0001-7247-2013","observed_orcids":["https://orcid.org/0000-0001-7247-2013"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Patel, Sandip","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":null,"display_name":":unav","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":":unav","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T13415","display_name":"Calcium signaling and nucleotide metabolism","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1314","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T13415","display_name":"Calcium signaling and nucleotide metabolism","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1314","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10493","display_name":"Ion channel regulation and function","score":0.00039999998989515007,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11204","display_name":"Ion Channels and Receptors","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2809","display_name":"Sensory Systems"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/tpc2","display_name":"TPC2","score":0.9950000047683716},{"id":"https://openalex.org/keywords/cation-selectivity","display_name":"cation selectivity","score":0.7590000033378601},{"id":"https://openalex.org/keywords/calcium-permeability","display_name":"calcium permeability","score":0.8320000171661377},{"id":"https://openalex.org/keywords/naadp","display_name":"NAADP","score":0.8700000047683716},{"id":"https://openalex.org/keywords/pi-3-5-p2","display_name":"PI(3,5)P2","score":0.9520000219345093},{"id":"https://openalex.org/keywords/allosteric-regulation","display_name":"allosteric regulation","score":0.7400000095367432},{"id":"https://openalex.org/keywords/caenorhabditis-elegans","display_name":"Caenorhabditis elegans","score":0.7770000100135803},{"id":"https://openalex.org/keywords/ion-channel-selectivity","display_name":"ion channel selectivity","score":0.5590000152587891}],"concepts":[{"id":"https://openalex.org/C2778938600","wikidata":"https://www.wikidata.org/wiki/Q389934","display_name":"Agonist","level":3,"score":0.8230000138282776},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7279999852180481},{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.7182999849319458},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.5764999985694885},{"id":"https://openalex.org/C43587935","wikidata":"https://www.wikidata.org/wiki/Q1258877","display_name":"Functional selectivity","level":4,"score":0.5454999804496765},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5303000211715698},{"id":"https://openalex.org/C50254741","wikidata":"https://www.wikidata.org/wiki/Q62536","display_name":"Ion channel","level":3,"score":0.5227000117301941},{"id":"https://openalex.org/C118792377","wikidata":"https://www.wikidata.org/wiki/Q108584245","display_name":"Selectivity","level":3,"score":0.5149999856948853},{"id":"https://openalex.org/C2780557392","wikidata":"https://www.wikidata.org/wiki/Q523796","display_name":"Linker","level":2,"score":0.4542999863624573},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.44190001487731934},{"id":"https://openalex.org/C98539663","wikidata":"https://www.wikidata.org/wiki/Q220599","display_name":"Cytosol","level":3,"score":0.41370001435279846},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.4122999906539917},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4052000045776367},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.4023999869823456},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.359499990940094},{"id":"https://openalex.org/C185263204","wikidata":"https://www.wikidata.org/wiki/Q1154774","display_name":"Electrophysiology","level":2,"score":0.2985999882221222},{"id":"https://openalex.org/C147944092","wikidata":"https://www.wikidata.org/wiki/Q176366","display_name":"Patch clamp","level":3,"score":0.29499998688697815},{"id":"https://openalex.org/C35341161","wikidata":"https://www.wikidata.org/wiki/Q289992","display_name":"Uniporter","level":4,"score":0.2935999929904938},{"id":"https://openalex.org/C79879829","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Intracellular","level":2,"score":0.2892000079154968},{"id":"https://openalex.org/C2779362680","wikidata":"https://www.wikidata.org/wiki/Q905000","display_name":"hERG","level":3,"score":0.2892000079154968},{"id":"https://openalex.org/C2776120743","wikidata":"https://www.wikidata.org/wiki/Q3271540","display_name":"Mechanism of action","level":3,"score":0.2858000099658966},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.28459998965263367},{"id":"https://openalex.org/C99975950","wikidata":"https://www.wikidata.org/wiki/Q911011","display_name":"Ion transporter","level":3,"score":0.28360000252723694},{"id":"https://openalex.org/C68709404","wikidata":"https://www.wikidata.org/wiki/Q1134475","display_name":"Flux (metallurgy)","level":2,"score":0.27709999680519104},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.2766999900341034},{"id":"https://openalex.org/C163235415","wikidata":"https://www.wikidata.org/wiki/Q899814","display_name":"Second messenger system","level":3,"score":0.274399995803833},{"id":"https://openalex.org/C193042331","wikidata":"https://www.wikidata.org/wiki/Q1772003","display_name":"Structure\u2013activity relationship","level":3,"score":0.26739999651908875},{"id":"https://openalex.org/C15152581","wikidata":"https://www.wikidata.org/wiki/Q7833966","display_name":"Transduction (biophysics)","level":2,"score":0.26669999957084656},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.25870001316070557},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.2556999921798706}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.24406/publica-9895","doi":"https://doi.org/10.24406/publica-9895","is_oa":true,"landing_page_url":"https://doi.org/10.24406/publica-9895","pdf_url":null,"source":{"id":"https://openalex.org/S4306400318","display_name":"Fraunhofer-Publica (Fraunhofer-Gesellschaft)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4923324","host_organization_name":"Fraunhofer-Gesellschaft","host_organization_lineage":["https://openalex.org/I4923324"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Other"}],"best_oa_location":{"id":"doi:10.24406/publica-9895","doi":"https://doi.org/10.24406/publica-9895","is_oa":true,"landing_page_url":"https://doi.org/10.24406/publica-9895","pdf_url":null,"source":{"id":"https://openalex.org/S4306400318","display_name":"Fraunhofer-Publica (Fraunhofer-Gesellschaft)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4923324","host_organization_name":"Fraunhofer-Gesellschaft","host_organization_lineage":["https://openalex.org/I4923324"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Other"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W3011823564","https://openalex.org/W4289521109","https://openalex.org/W4388219136","https://openalex.org/W4386065146","https://openalex.org/W4401071031","https://openalex.org/W4407841667","https://openalex.org/W4207084828","https://openalex.org/W6910771207","https://openalex.org/W2798173301","https://openalex.org/W2995976751"],"abstract_inverted_index":{"Ion":[0],"channels":[1,17],"possess":[2],"selectivity":[3,28,188],"filters":[4],"that":[5,83,131,183],"are":[6,18,22,184],"hardwired":[7],"to":[8,24,42,99,106,135],"ensure":[9],"the":[10,47,57,69,89,95,100,115,133,136,187],"selective":[11],"passage":[12],"of":[13,36,85,117,129],"ions.":[14],"Lysosomal":[15],"two-pore":[16],"unusual":[19],"as":[20],"they":[21],"able":[23],"switch":[25],"their":[26],"cation":[27],"in":[29,114,154,164,169,172],"an":[30],"agonist-specific":[31],"manner,":[32],"allowing":[33],"differential":[34],"control":[35],"organellar":[37],"activity.":[38],"TPC2":[39,86,103,177],"is":[40,76],"permeable":[41],"Ca2+":[43,145,191],"when":[44,54,152],"activated":[45,55],"by":[46,56,125],"calcium-mobilizing":[48],"messenger":[49],"NAADP,":[50],"but":[51,64],"largely":[52,104],"Na+-selective":[53],"signaling":[58,175],"lipid":[59],"PI(3,5)P2.":[60,118],"Co-stimulation":[61],"increases":[62],"Ca02+":[63],"not":[65,77],"Na+":[66],"permeability;":[67],"however,":[68],"molecular":[70,181],"basis":[71],"for":[72],"these":[73],"specificity":[74],"switches":[75],"well":[78],"understood.":[79],"Here":[80],"we":[81],"show":[82],"mutation":[84,120,160],"residues":[87,130],"within":[88],"distal":[90],"cytosolic":[91],"linker,":[92],"which":[93],"connects":[94,132],"first":[96],"voltage-sensing-like":[97],"domain":[98],"pore,":[101],"rendered":[102],"unable":[105],"discriminate":[107],"its":[108],"agonists":[109],"and":[110,147,150,171,195],"highly":[111],"calcium-permeable,":[112],"even":[113],"presence":[116],"This":[119],"induced":[121],"a":[122,127,165],"co-activated-like":[123],"state":[124],"disrupting":[126],"network":[128],"linker":[134],"activation":[137],"gate.":[138],"Such":[139],"deregulated":[140],"agonist":[141,162],"action":[142,163],"increased":[143],"lysosomal":[144],"flux":[146],"compromised":[148],"locomotion":[149],"viability":[151],"expressed":[153],"C.":[155],"elegans.":[156],"A":[157],"proximal":[158],"disease-linked":[159],"perturbed":[161],"similar":[166],"way":[167],"both":[168],"vitro":[170],"vivo.":[173],"Biased":[174],"through":[176,180],"thus":[178],"proceeds":[179],"determinants":[182],"remote":[185],"from":[186],"filter,":[189],"affecting":[190],"permeability,":[192],"endo-lysosomal":[193],"integrity":[194],"disease.":[196]},"counts_by_year":[],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-08-20T00:00:00"}
