{"doi":"10.1016/j.cell.2025.12.005","title":"Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex","abstract":null,"journal":"Cell","year":2026,"id":612115,"datarank":0.31758137647770573,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0056651452257303215,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0056651452257303215,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":6,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1370960,"name":"Charles Bayly-Jones","orcid":"0000-0002-7573-7715","position":1,"is_corresponding":false},{"id":1575883,"name":"Shuqi Dong","orcid":null,"position":2,"is_corresponding":false},{"id":1575884,"name":"Terrance Lam","orcid":null,"position":3,"is_corresponding":false},{"id":1575885,"name":"Wentong Luo","orcid":null,"position":4,"is_corresponding":false},{"id":1575886,"name":"Gareth D. 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Lupton","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex","abstract":"The guanosine triphosphate (GTP)-bound state of the heterodimeric Rag GTPases functions as a molecular switch regulating mechanistic target of rapamycin complex 1 (mTORC1) activation at the lysosome downstream of amino acid fluctuations. Under low amino acid conditions, GTPase-activating protein (GAP) activity toward Rags 1 (GATOR1) promotes RagA GTP hydrolysis, preventing mTORC1 activation. KICSTOR recruits and regulates GATOR1 at the lysosome by undefined mechanisms. Here, we resolve the KICSTOR-GATOR1 structure, revealing a striking ∼60-nm crescent-shaped assembly. GATOR1 anchors to KICSTOR via an extensive interface, and mutations that disrupt this interaction impair mTORC1 regulation. The S-adenosylmethionine sensor SAMTOR binds KICSTOR in a manner incompatible with metabolite binding, providing structural insight into methionine sensing via SAMTOR-KICSTOR association. We discover that KICSTOR and GATOR1 form a dimeric supercomplex. This assembly restricts GATOR1 to an orientation that favors the low-affinity active GAP mode of Rag GTPase engagement while sterically restricting access to the high-affinity inhibitory mode, consistent with a model of an active lysosomal GATOR1 docking complex.","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41512879","pmcid":null,"openalex_id":"https://openalex.org/W7119513046","authors":[],"funders":[{"funder_name":"Victorian Cancer Agency","grant_id":"","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"","title":null},{"funder_name":"Sylvia and Charles Viertel Charitable Foundation","grant_id":"","title":null},{"funder_name":"Australian Research Council","grant_id":"","title":null}],"total_grants":4,"fwci":25.0659,"citation_percentile":0.99585097,"influential_citations":0,"citation_trend":[{"year":2026,"count":6}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.cell.2025.12.005","host_type":"journal"},{"url":"https://doi.org/10.1016/j.cell.2025.12.005","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0092867425014187?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0092867425014187?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41512879","host_type":"repository"}],"fields_of_study":["PI3K/AKT/mTOR signaling in cancer","Cellular transport and secretion","Microtubule and mitosis dynamics","Lysosomes","Mechanistic Target of Rapamycin Complex 1","GTPase-Activating Proteins","Monomeric GTP-Binding Proteins","Humans","Animals","S-Adenosylmethionine","Guanosine Triphosphate","Models, Molecular","Protein Binding"],"mesh_terms":["Mechanistic Target of Rapamycin Complex 1","Nutrients","Animals","Guanosine Triphosphate","Humans","Lysosomes","Models, Molecular","Protein Binding","S-Adenosylmethionine","Monomeric GTP-Binding Proteins","GTPase-Activating Proteins","HEK293 Cells"],"keywords":["GTPase","mTORC1","Lysosome","Guanosine triphosphate","Guanosine","Amino acid","GTP'","Adenosine triphosphate","Docking (animal)","Triphosphatase","Cell metabolism","S-Adenosylmethionine","Cryo-em","Gator1","Rag Gtpase","Szt2","Samtor","Kicstor","Rag-ragulator"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T01:37:59.697962Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}