{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:06:53Z","timestamp":1788498413634,"version":"build-2803163510"},"reference-count":31,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Molecular Biology"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.jmb.2020.166743","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T12:00:08Z","timestamp":1607428808000},"page":"166743","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":34,"title":["Architecture of the Tuberous Sclerosis Protein Complex"],"prefix":"10.1016","volume":"433","author":[{"given":"Kailash","family":"Ramlaul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencheng","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e0lia","family":"de Martin Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjari","family":"Trivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.S.","family":"Aylett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jmb.2020.166743_b0005","doi-asserted-by":"crossref","first-page":"16035","DOI":"10.1038\/nrdp.2016.35","article-title":"Tuberous sclerosis complex","volume":"2","author":"Henske","year":"2016","journal-title":"Nature Rev. Dis. Prim."},{"key":"10.1016\/j.jmb.2020.166743_b0010","doi-asserted-by":"crossref","first-page":"35647","DOI":"10.1074\/jbc.274.50.35647","article-title":"Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin","volume":"274","author":"Nellist","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2020.166743_b0015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0093940","article-title":"Identification of regions critical for the integrity of the TSC1-TSC2-TBC1D7 complex","volume":"9","author":"Santiago Lima","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jmb.2020.166743_b0020","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/hmg\/7.6.1053","article-title":"Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products","volume":"7","author":"van Slegtenhorst","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.jmb.2020.166743_b0025","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.molcel.2012.06.009","article-title":"TBC1D7 is a third subunit of the TSC1}-{TSC2 complex upstream of {mTORC1}","volume":"47","author":"Dibble","year":"2012","journal-title":"Mol. Cell."},{"key":"10.1016\/j.jmb.2020.166743_b0030","doi-asserted-by":"crossref","first-page":"397","DOI":"10.15252\/embj.201696010","article-title":"Nutrient sensing and TOR signaling in yeast and mammals","volume":"36","author":"Gonz\u00e1lez","year":"2017","journal-title":"EMBO J."},{"key":"10.1016\/j.jmb.2020.166743_b0035","first-page":"1","article-title":"Signal integration in the (m)TORC1 growth pathway","author":"Ramlaul","year":"2018","journal-title":"Front. Biol. (Beijing)"},{"key":"10.1016\/j.jmb.2020.166743_b0040","doi-asserted-by":"crossref","first-page":"10608","DOI":"10.1074\/jbc.272.16.10608","article-title":"The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation","volume":"272","author":"Clark","year":"1997","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2020.166743_b0045","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nature25023","article-title":"Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40","volume":"552","author":"Yang","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.jmb.2020.166743_b0050","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1}-{TSC2 complex: a molecular switchboard controlling cell growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem. J."},{"key":"10.1016\/j.jmb.2020.166743_b0055","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cell.2013.11.049","article-title":"Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome","volume":"156","author":"Menon","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.jmb.2020.166743_b0060","doi-asserted-by":"crossref","first-page":"10662","DOI":"10.1038\/ncomms10662","article-title":"Lysosomal recruitment of TSC2 is a universal response to cellular stress","volume":"7","author":"Demetriades","year":"2016","journal-title":"Nature Commun."},{"key":"10.1016\/j.jmb.2020.166743_b0065","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1074\/jbc.C200499200","article-title":"14\u20133-3\u03b2 binds to and negatively regulates the tuberous sclerosis complex 2 ({TSC2}) tumor suppressor gene product, tuberin","volume":"278","author":"Shumway","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2020.166743_b0070","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1083\/jcb.200507119","article-title":"Activity of TSC2 is inhibited by {AKT}-mediated phosphorylation and membrane partitioning","volume":"173","author":"Cai","year":"2006","journal-title":"J. Cell. Biol."},{"key":"10.1016\/j.jmb.2020.166743_b0075","doi-asserted-by":"crossref","first-page":"6306","DOI":"10.1038\/sj.onc.1204009","article-title":"The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination","volume":"19","author":"Benvenuto","year":"2000","journal-title":"Oncogene"},{"key":"10.1016\/j.jmb.2020.166743_b0080","doi-asserted-by":"crossref","first-page":"8313","DOI":"10.1074\/jbc.C500451200","article-title":"TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase","volume":"281","author":"Chong-Kopera","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2020.166743_b0085","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1038\/ncomms3135","article-title":"Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations","volume":"4","author":"Sun","year":"2013","journal-title":"Nature Commun."},{"key":"10.1016\/j.jmb.2020.166743_b0090","doi-asserted-by":"crossref","first-page":"20008","DOI":"10.1074\/jbc.M116.732446","article-title":"Structure of the Tuberous Sclerosis Complex 2 ({TSC2}) N terminus provides insight into complex assembly and tuberous sclerosis pathogenesis","volume":"291","author":"Zech","year":"2016","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jmb.2020.166743_b0095","doi-asserted-by":"crossref","DOI":"10.1016\/j.str.2020.05.008","article-title":"Structural analysis of the TSC2 GAP domain: mechanistic insight into catalysis and pathogenic mutations","author":"Hansmann","year":"2020","journal-title":"Structure"},{"key":"10.1016\/j.jmb.2020.166743_b0100","doi-asserted-by":"crossref","DOI":"10.1093\/jmcb\/mjw001","article-title":"Structure of the TBC1D7}-{TSC1 complex reveals that TBC1D7 stabilizes dimerization of the TSC1 C-terminal coiled coil region","author":"Gai","year":"2016","journal-title":"J. Mol. Cell. Biol."},{"key":"10.1016\/j.jmb.2020.166743_b0105","doi-asserted-by":"crossref","first-page":"8591","DOI":"10.1074\/jbc.M115.701870","article-title":"Structural basis of the interaction between Tuberous Sclerosis Complex 1 ({TSC1}) and Tre2-Bub2-Cdc16 Domain Family Member 7 ({TBC1D7})","volume":"291","author":"Qin","year":"2016","journal-title":"J Biol Chem."},{"key":"10.1016\/j.jmb.2020.166743_b0110","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/emboj.2008.30","article-title":"The Rap-{RapGAP} complex: GTP hydrolysis without catalytic glutamine and arginine residues","volume":"27","author":"Scrima","year":"2008","journal-title":"EMBO J."},{"key":"10.1016\/j.jmb.2020.166743_b0115","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.bbadis.2010.06.004","article-title":"Analysis of TSC1 truncations defines regions involved in TSC1 stability, aggregation and interaction","volume":"1802","author":"Hoogeveen-Westerveld","year":"2010","journal-title":"Biochim. Biophys. Acta - Mol. Basis Dis."},{"key":"10.1016\/j.jmb.2020.166743_b0120","doi-asserted-by":"crossref","DOI":"10.15252\/embj.201796700","article-title":"Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients","volume":"36","author":"Woodford","year":"2017","journal-title":"EMBO J."},{"key":"10.1016\/j.jmb.2020.166743_b0125","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nmeth.4193","article-title":"MotionCor2: Anisotropic correction of beam-induced motion for improved cryo-electron microscopy","volume":"14","author":"Zheng","year":"2017","journal-title":"Nature Methods"},{"key":"10.1016\/j.jmb.2020.166743_b0130","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jsb.2015.08.008","article-title":"CTFFIND4: fast and accurate defocus estimation from electron micrographs","volume":"192","author":"Rohou","year":"2015","journal-title":"J. Struct. Biol."},{"key":"10.1016\/j.jmb.2020.166743_b0135","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jsb.2006.05.009","article-title":"EMAN2: an extensible image processing suite for electron microscopy","volume":"157","author":"Tang","year":"2007","journal-title":"J. Struct. Biol."},{"key":"10.1016\/j.jmb.2020.166743_b0140","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","article-title":"RELION: Implementation of a Bayesian approach to cryo-EM structure determination","volume":"180","author":"Scheres","year":"2012","journal-title":"J. Struct. Biol."},{"key":"10.1016\/j.jmb.2020.166743_b0145","article-title":"RELION-3: new tools for automated high-resolution cryo-EM structure determination","volume":"7","author":"Zivanov","year":"2018","journal-title":"BioRxiv"},{"key":"10.1016\/j.jmb.2020.166743_b0150","first-page":"245","article-title":"Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs","volume":"10812","author":"Bepler","year":"2018","journal-title":"Nature Methods"},{"key":"10.1016\/j.jmb.2020.166743_b0155","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."}],"container-title":["Journal of Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022283620306689?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022283620306689?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T21:39:24Z","timestamp":1758317964000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022283620306689"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["S0022283620306689"],"URL":"https:\/\/doi.org\/10.1016\/j.jmb.2020.166743","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.739197469.793583245","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.09.29.319707","asserted-by":"object"}]},"ISSN":["0022-2836"],"issn-type":[{"value":"0022-2836","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Architecture of the Tuberous Sclerosis Protein Complex","name":"articletitle","label":"Article Title"},{"value":"Journal of Molecular Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jmb.2020.166743","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"166743"}}