{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:22:46Z","timestamp":1791685366164,"version":"4.3.4"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["APP1157348"],"award-info":[{"award-number":["APP1157348"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020492","name":"Translational Research Institute","doi-asserted-by":"publisher","award":["QLD 4102"],"award-info":[{"award-number":["QLD 4102"]}],"id":[{"id":"10.13039\/501100020492","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Translational Research Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glycoprotein 130 (GP130) is an archetypal class I cytokine receptor that serves as a shared signalling subunit for a group of cytokines known as interleukin 6 (IL-6)-type cytokines. GP130 does not have an intrinsic kinase activity and relies on Janus kinases (JAK) 1, 2, or Tyrosine kinase 2 (TYK2) for phosphorylation of tyrosine residues on its cytoplasmic domain for signal transduction. In this study we investigated the molecular mechanism of GP130 activation. We utilized GP130 constructs that were held in varying states of activation by replacing the entire extracellular region of the receptor with a leucine zipper dimerisation domain and inserted alanine residues into the extracellular juxtamembrane linker sequence to induce rotation of the transmembrane domains. These chimeras differentially activated the associated JAK2 molecules which also correlated with receptor tyrosine phosphorylation status. F\u00f6rster resonance energy transfer (FRET) microscopy in live cells was used to show that GP130 cytoplasmic domains were in close proximity in active chimeras compared to the inactive receptors, presumably to facilitate JAK protein activation. Coarse-grained molecular dynamics simulations provided a structural rationale for this register-dependent mechanism, showing that active chimeras preferentially maintain compact transmembrane packing and reduced membrane-proximal cytosolic spacing, whereas signalling-deficient constructs sample more heterogeneous transmembrane geometries and increased cytosolic separation. Finally, mutational analysis identified the negatively charged juxtamembrane residues E617 and E619 as critical for signal transduction; charge reversal at these positions in the full-length receptor generated a dominant-negative GP130 variant devoid of signalling capacity.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag118","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:24:08Z","timestamp":1781796248000},"source":"Crossref","is-referenced-by-count":1,"title":["Transmembrane orientation and extracellular juxtamembrane residues of GP130 are critical for signal transduction"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6485-9952","authenticated-orcid":false,"given":"Farhad","family":"Dehkhoda","sequence":"first","affiliation":[{"name":"The Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane,","place":["Australia"]},{"name":"School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2883-4675","authenticated-orcid":false,"given":"Yash","family":"Chhabra","sequence":"additional","affiliation":[{"name":"The Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane,","place":["Australia"]},{"name":"Fox Chase Cancer Center , 333 Cottman Avenue , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0791-6850","authenticated-orcid":false,"given":"Fiona","family":"Whelan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Science, School of Biological Sciences, Adelaide University , Adelaide, SA,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-9840","authenticated-orcid":false,"given":"Cameron J","family":"Nowell","sequence":"additional","affiliation":[{"name":"Drug Discovery Biology and Department of Pharmacology, Monash University , Melbourne,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5242-6789","authenticated-orcid":false,"given":"Matthew J","family":"Morris","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8655-8221","authenticated-orcid":false,"given":"Sebastian G B","family":"Furness","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane,","place":["Australia"]},{"name":"Drug Discovery Biology and Department of Pharmacology, Monash University , Melbourne,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-1668","authenticated-orcid":false,"given":"Andrew J","family":"Brooks","sequence":"additional","affiliation":[{"name":"The Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane,","place":["Australia"]},{"name":"School of Science & Technology, University of New England , Armidale, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"2026090708323211400_vkag118-B1","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1093\/emboj\/19.11.2399","article-title":"Receptor recognition by gp130 cytokines","volume":"19","author":"Bravo","year":"2000","journal-title":"Embo J"},{"key":"2026090708323211400_vkag118-B2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1146\/annurev.bi.65.070196.003141","article-title":"Hematopoietic receptor complexes","volume":"65","author":"Wells","year":"1996","journal-title":"Annu Rev Biochem"},{"key":"2026090708323211400_vkag118-B3","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0065-3233(08)60433-7","article-title":"Structural basis for cytokine hormone-receptor recognition and receptor activation","volume":"52","author":"Kossiakoff","year":"1998","journal-title":"Adv Protein Chem"},{"key":"2026090708323211400_vkag118-B4","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1182\/blood.V87.5.1851.1851","article-title":"Six different cytokines that share GP130 as a receptor subunit, induce serum amyloid A and potentiate the induction of interleukin-6 and the activation of the hypothalamus-pituitary-adrenal axis by interleukin-1","volume":"87","author":"Benigni","year":"1996","journal-title":"Blood."},{"key":"2026090708323211400_vkag118-B5","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.4049\/jimmunol.172.4.2225","article-title":"WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27","volume":"172","author":"Pflanz","year":"2004","journal-title":"J Immunol"},{"key":"2026090708323211400_vkag118-B6","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.str.2007.02.006","article-title":"The dynamics of signal triggering in a gp130-receptor complex","volume":"15","author":"Matadeen","year":"2007","journal-title":"Structure"},{"key":"2026090708323211400_vkag118-B7","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.molcel.2008.08.011","article-title":"Structural organization of a full-length gp130\/LIF-R cytokine receptor transmembrane complex","volume":"31","author":"Skiniotis","year":"2008","journal-title":"Mol Cell"},{"key":"2026090708323211400_vkag118-B8","doi-asserted-by":"crossref","first-page":"6215","DOI":"10.1016\/S0021-9258(17)37590-7","article-title":"Oncostatin M and leukemia inhibitory factor trigger overlapping and different signals through partially shared receptor complexes","volume":"269","author":"Thoma","year":"1994","journal-title":"J Biol Chem"},{"key":"2026090708323211400_vkag118-B9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0014-5793(95)00053-C","article-title":"The membrane distal half of gp130 is responsible for the formation of a ternary complex with IL-6 and the IL-6 receptor","volume":"360","author":"Horsten","year":"1995","journal-title":"FEBS Lett"},{"key":"2026090708323211400_vkag118-B10","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1093\/emboj\/17.6.1665","article-title":"Crystal structure of a cytokine-binding region of gp130","volume":"17","author":"Bravo","year":"1998","journal-title":"Embo J"},{"key":"2026090708323211400_vkag118-B11","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1126\/science.1058308","article-title":"Structure of an extracellular gp130 cytokine receptor signaling complex","volume":"291","author":"Chow","year":"2001","journal-title":"Science."},{"key":"2026090708323211400_vkag118-B12","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1126\/science.1083901","article-title":"Hexameric structure and assembly of the interleukin-6\/IL-6 alpha-receptor\/gp130 complex","volume":"300","author":"Boulanger","year":"2003","journal-title":"Science."},{"key":"2026090708323211400_vkag118-B13","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nsmb941","article-title":"Signaling conformations of the tall cytokine receptor gp130 when in complex with IL-6 and IL-6 receptor","volume":"12","author":"Skiniotis","year":"2005","journal-title":"Nat Struct Mol Biol"},{"key":"2026090708323211400_vkag118-B14","doi-asserted-by":"crossref","first-page":"21214","DOI":"10.1074\/jbc.C110.129502","article-title":"Crystal structure of the entire ectodomain of gp130: insights into the molecular assembly of the tall cytokine receptor complexes","volume":"285","author":"Xu","year":"2010","journal-title":"J Biol Chem"},{"key":"2026090708323211400_vkag118-B15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.str.2010.10.010","article-title":"Structural snapshots of full-length Jak1, a transmembrane gp130\/IL-6\/IL-6Ralpha cytokine receptor complex, and the receptor-Jak1 holocomplex","volume":"19","author":"Lupardus","year":"2011","journal-title":"Structure."},{"key":"2026090708323211400_vkag118-B16","doi-asserted-by":"crossref","first-page":"eade4395","DOI":"10.1126\/sciadv.ade4395","article-title":"Structural insights into the assembly of gp130 family cytokine signaling complexes","volume":"9","author":"Zhou","year":"2023","journal-title":"Sci Adv."},{"key":"2026090708323211400_vkag118-B17","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1126\/science.2683088","article-title":"Scissors-grip model for DNA recognition by a family of leucine zipper proteins","volume":"246","author":"Vinson","year":"1989","journal-title":"Science."},{"key":"2026090708323211400_vkag118-B18","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/373257a0","article-title":"Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA","volume":"373","author":"Glover","year":"1995","journal-title":"Nature"},{"key":"2026090708323211400_vkag118-B19","doi-asserted-by":"crossref","first-page":"17000","DOI":"10.1074\/jbc.275.22.17000","article-title":"Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation","volume":"275","author":"Behncken","year":"2000","journal-title":"J Biol Chem"},{"key":"2026090708323211400_vkag118-B20","doi-asserted-by":"crossref","first-page":"1249783","DOI":"10.1126\/science.1249783","article-title":"Mechanism of activation of protein kinase JAK2 by the growth hormone receptor","volume":"344","author":"Brooks","year":"2014","journal-title":"Science."},{"key":"2026090708323211400_vkag118-B21","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1091\/mbc.e05-12-1129","article-title":"Forced dimerization of gp130 leads to constitutive STAT3 activation, cytokine-independent growth, and blockade of differentiation of embryonic stem cells","volume":"17","author":"Stuhlmann-Laeisz","year":"2006","journal-title":"Mol Biol Cell."},{"key":"2026090708323211400_vkag118-B22","doi-asserted-by":"crossref","first-page":"30386","DOI":"10.1074\/jbc.271.48.30386","article-title":"Functional replacement of cytokine receptor extracellular domains by leucine zippers","volume":"271","author":"Patel","year":"1996","journal-title":"J Biol Chem"},{"key":"2026090708323211400_vkag118-B23","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41551-023-01143-w","article-title":"Modular chimeric cytokine receptors with leucine zippers enhance the antitumour activity of CAR T cells via JAK\/STAT signalling","volume":"8","author":"Bell","year":"2024","journal-title":"Nat Biomed Eng."},{"key":"2026090708323211400_vkag118-B24","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1074\/jbc.M115.686071","article-title":"Type I interferon signaling is decoupled from specific receptor orientation through lenient requirements of the transmembrane domain","volume":"291","author":"Sharma","year":"2016","journal-title":"J Biol Chem"},{"key":"2026090708323211400_vkag118-B25","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S1097-2765(01)00185-X","article-title":"The erythropoietin receptor cytosolic juxtamembrane domain contains an essential, precisely oriented, hydrophobic motif","volume":"7","author":"Constantinescu","year":"2001","journal-title":"Mol Cell."},{"key":"2026090708323211400_vkag118-B26","doi-asserted-by":"crossref","first-page":"26959","DOI":"10.1074\/jbc.M204113200","article-title":"Orientational constraints of the gp130 intracellular juxtamembrane domain for signaling","volume":"277","author":"Greiser","year":"2002","journal-title":"J Biol Chem"},{"key":"2026090708323211400_vkag118-B27","doi-asserted-by":"crossref","first-page":"e6441","DOI":"10.1371\/journal.pone.0006441","article-title":"Circular polymerase extension cloning of complex gene libraries and pathways","volume":"4","author":"Quan","year":"2009","journal-title":"PLoS One."},{"key":"2026090708323211400_vkag118-B28","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nprot.2010.181","article-title":"Circular polymerase extension cloning for high-throughput cloning of complex and combinatorial DNA libraries","volume":"6","author":"Quan","year":"2011","journal-title":"Nat Protoc"},{"key":"2026090708323211400_vkag118-B29","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1242\/jcs.001404","article-title":"A FRET map of membrane anchors suggests distinct microdomains of heterotrimeric G proteins","volume":"120","author":"Abankwa","year":"2007","journal-title":"J Cell Sci"},{"key":"2026090708323211400_vkag118-B30","doi-asserted-by":"crossref","first-page":"112490","DOI":"10.1016\/j.celrep.2023.112490","article-title":"Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation","volume":"42","author":"Chhabra","year":"2023","journal-title":"Cell Rep"},{"key":"2026090708323211400_vkag118-B31","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/sj.gt.3301206","article-title":"Plat-E: an efficient and stable system for transient packaging of retroviruses","volume":"7","author":"Morita","year":"2000","journal-title":"Gene Ther"},{"key":"2026090708323211400_vkag118-B32","doi-asserted-by":"crossref","first-page":"4949","DOI":"10.1073\/pnas.80.16.4949","article-title":"Generation of protein-reactive antibodies by short peptides is an event of high frequency: implications for the structural basis of immune recognition","volume":"80","author":"Niman","year":"1983","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2026090708323211400_vkag118-B33","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"2026090708323211400_vkag118-B34","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.3892\/etm.2014.1928","article-title":"Fluorescence resonance energy transfer detection methods: Sensitized emission and acceptor bleaching","volume":"8","author":"Qian","year":"2014","journal-title":"Exp Ther Med."},{"key":"2026090708323211400_vkag118-B35","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"2026090708323211400_vkag118-B36","doi-asserted-by":"crossref","first-page":"4200","DOI":"10.21105\/joss.04200","article-title":"GEMMI: A library for structural biology","volume":"7","author":"Wojdyr","year":"2022","journal-title":"JOSS"},{"key":"2026090708323211400_vkag118-B37","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.90627.4","article-title":"Martinize2 and Vermouth provide a unified framework for molecular topology generation","volume":"12","author":"Kroon","year":"2025","journal-title":"Elife"},{"key":"2026090708323211400_vkag118-B38","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41592-021-01098-3","article-title":"Martini 3: a general purpose force field for coarse-grained molecular dynamics","volume":"18","author":"Souza","year":"2021","journal-title":"Nat Methods"},{"key":"2026090708323211400_vkag118-B39","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1021\/acs.jctc.5b00209","article-title":"Computational lipidomics with insane: a versatile tool for generating custom membranes for molecular simulations","volume":"11","author":"Wassenaar","year":"2015","journal-title":"J Chem Theory Comput"},{"key":"2026090708323211400_vkag118-B40","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/(SICI)1521-3773(19990115)38:1\/2<236::AID-ANIE236>3.0.CO;2-M","article-title":"Peptide folding: when simulation meets experiment","volume":"38","author":"Daura","year":"1999","journal-title":"Angew Chem Int Ed"},{"key":"2026090708323211400_vkag118-B41","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1126\/science.abn8933","article-title":"Structure of a Janus kinase cytokine receptor complex reveals the basis for dimeric activation","volume":"376","author":"Glassman","year":"2022","journal-title":"Science."},{"key":"2026090708323211400_vkag118-B42","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2174\/138161211795164202","article-title":"The gp130 receptor cytokine family: regulators of adipocyte development and function","volume":"17","author":"White","year":"2011","journal-title":"Curr Pharm Des"},{"key":"2026090708323211400_vkag118-B43","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1073\/pnas.91.3.1119","article-title":"Proliferative responses and binding properties of hematopoietic cells transfected with low-affinity receptors for leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor","volume":"91","author":"Gearing","year":"1994","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2026090708323211400_vkag118-B44","doi-asserted-by":"crossref","first-page":"23748","DOI":"10.1074\/jbc.272.38.23748","article-title":"Molecular modeling-guided mutagenesis of the extracellular part of gp130 leads to the identification of contact sites in the interleukin-6 (IL-6).IL-6 receptor.gp130 complex","volume":"272","author":"Horsten","year":"1997","journal-title":"J Biol Chem"},{"key":"2026090708323211400_vkag118-B45","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1359-6101(98)80005-1","article-title":"Signaling mechanisms through gp130: a model of the cytokine system","volume":"8","author":"Hirano","year":"1997","journal-title":"Cytokine Growth Factor Rev"},{"key":"2026090708323211400_vkag118-B46","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/nbt0297-142","article-title":"I. A bioactive designer cytokine for human hematopoietic progenitor cell expansion","volume":"15","author":"Fischer","year":"1997","journal-title":"Nat Biotechnol"},{"key":"2026090708323211400_vkag118-B47","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1074\/jbc.274.3.1257","article-title":"The designer cytokine hyper-interleukin-6 is a potent activator of STAT3-dependent gene transcription in vivo and in vitro","volume":"274","author":"Rakemann","year":"1999","journal-title":"J Biol Chem"},{"key":"2026090708323211400_vkag118-B48","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ghir.2015.06.001","article-title":"The growth hormone receptor","volume":"28","author":"Waters","year":"2016","journal-title":"Growth Horm IGF Res"},{"key":"2026090708323211400_vkag118-B49","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/15476910601154779","article-title":"Mechanisms of signal transduction from receptors of Type I and Type II cytokines","volume":"4","author":"Fujii","year":"2007","journal-title":"J Immunotoxicol"},{"key":"2026090708323211400_vkag118-B50","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nsmb.2807","article-title":"Structural basis of recognition of interferon-alpha receptor by tyrosine kinase 2","volume":"21","author":"Wallweber","year":"2014","journal-title":"Nat Struct Mol Biol"},{"key":"2026090708323211400_vkag118-B51","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.str.2016.03.023","article-title":"The structural basis for class II cytokine receptor recognition by JAK1","volume":"24","author":"Ferrao","year":"2016","journal-title":"Structure."},{"key":"2026090708323211400_vkag118-B52","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s11064-012-0741-1","article-title":"Spatial organization and stoichiometry of N-terminal domain-mediated glycosyltransferase complexes in Golgi membranes determined by fret microscopy","volume":"37","author":"Ferrari","year":"2012","journal-title":"Neurochem Res"},{"key":"2026090708323211400_vkag118-B53","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev-immunol-032713-120211","article-title":"Insights into cytokine-receptor interactions from cytokine engineering","volume":"33","author":"Spangler","year":"2015","journal-title":"Annu Rev Immunol"},{"key":"2026090708323211400_vkag118-B54","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41577-023-00856-y","article-title":"Targeting IL-6 trans-signalling: past, present and future prospects","volume":"23","author":"Rose-John","year":"2023","journal-title":"Nat Rev Immunol."},{"key":"2026090708323211400_vkag118-B55","doi-asserted-by":"crossref","first-page":"3604","DOI":"10.1046\/j.1432-1327.2000.01389.x","article-title":"Human herpes virus 8 interleukin-6 homologue triggers gp130 on neuronal and hematopoietic cells","volume":"267","author":"Hoischen","year":"2000","journal-title":"Eur J Biochem"},{"key":"2026090708323211400_vkag118-B56","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/1043-4666(92)90043-Q","article-title":"Isolation of an mRNA encoding a soluble form of the human interleukin-6 receptor","volume":"4","author":"Lust","year":"1992","journal-title":"Cytokine"},{"key":"2026090708323211400_vkag118-B57","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/eji.1830230226","article-title":"The soluble interleukin-6 receptor is generated by shedding","volume":"23","author":"Mullberg","year":"1993","journal-title":"Eur J Immunol"},{"key":"2026090708323211400_vkag118-B58","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/ni.2227","article-title":"The composition and signaling of the IL-35 receptor are unconventional","volume":"13","author":"Collison","year":"2012","journal-title":"Nat Immunol"},{"key":"2026090708323211400_vkag118-B59","doi-asserted-by":"crossref","first-page":"12043","DOI":"10.1038\/s41598-019-48541-2","article-title":"A comprehensive computational study of amino acid interactions in membrane proteins","volume":"9","author":"Mbaye","year":"2019","journal-title":"Sci Rep."},{"key":"2026090708323211400_vkag118-B60","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/nsmb977","article-title":"Model for growth hormone receptor activation based on subunit rotation within a receptor dimer","volume":"12","author":"Brown","year":"2005","journal-title":"Nat Struct Mol Biol"},{"key":"2026090708323211400_vkag118-B61","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4049\/jimmunol.164.1.273","article-title":"Importance of the membrane-proximal extracellular domains for activation of the signal transducer glycoprotein 130","volume":"164","author":"Kurth","year":"2000","journal-title":"J Immunol."},{"key":"2026090708323211400_vkag118-B62","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1046\/j.1432-1033.2002.02941.x","article-title":"A functional role of the membrane-proximal extracellular domains of the signal transducer gp130 in heterodimerization with the leukemia inhibitory factor receptor","volume":"269","author":"Timmermann","year":"2002","journal-title":"Eur J Biochem"},{"key":"2026090708323211400_vkag118-B63","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1038\/s41467-024-46235-6","article-title":"Structural insights into IL-11-mediated signalling and human IL6ST variant-associated immunodeficiency","volume":"15","author":"Gardner","year":"2024","journal-title":"Nat Commun"},{"key":"2026090708323211400_vkag118-B64","doi-asserted-by":"crossref","first-page":"7543","DOI":"10.1038\/s41467-023-42754-w","article-title":"Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant","volume":"14","author":"Metcalfe","year":"2023","journal-title":"Nat Commun"},{"key":"2026090708323211400_vkag118-B65","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.38089","article-title":"Receptor-mediated dimerization of JAK2 FERM domains is required for JAK2 activation","volume":"7","author":"Ferrao","year":"2018","journal-title":"Elife"},{"key":"2026090708323211400_vkag118-B66","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1016\/j.jmb.2016.10.005","article-title":"Crystal structure of a complex of the intracellular domain of interferon lambda receptor 1 (IFNLR1) and the FERM\/SH2 domains of human JAK1","volume":"428","author":"Zhang","year":"2016","journal-title":"J Mol Biol"},{"key":"2026090708323211400_vkag118-B67","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1-2","author":"Abraham","year":"2015","journal-title":"SoftwareX."},{"key":"2026090708323211400_vkag118-B68","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1107\/S0907444911007281","article-title":"Presenting your structures: the CCP4mg molecular-graphics software","volume":"67","author":"McNicholas","year":"2011","journal-title":"Acta Crystallogr D Biol Crystallogr."},{"key":"2026090708323211400_vkag118-B69","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/6\/vkag118\/68548623\/vkag118.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/6\/vkag118\/68548623\/vkag118.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:32:45Z","timestamp":1788784365000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/doi\/10.1093\/jimmun\/vkag118\/8711054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":69,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,7]]}},"URL":"https:\/\/doi.org\/10.1093\/jimmun\/vkag118","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,6]]},"article-number":"vkag118"}}