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IL\u201011 also has pathological roles in chronic inflammatory diseases, fibrosis, and cancer. In this structural snapshot, we explore our recently published cryo\u2010EM structure of the human IL\u201011 signalling complex to understand the molecular mechanisms of complex formation and disease\u2010associated mutations. IL\u201011 signals by binding to its cell surface receptors, the IL\u201011 receptor \u03b1 subunit (IL\u201011R\u03b1) and glycoprotein 130 (gp130), to form a hexameric signalling complex. We examine the locations within the complex of receptor sequence variants that are associated with craniosynostosis and craniosynostosis\u2010like phenotypes and speculate on potential molecular mechanisms leading to defects in signalling function. While these causative amino acid sequence changes in IL\u201011R\u03b1 are generally distal to interfaces between components of the complex, important structural residues are highly represented, including proline residues, cysteine residues involved in disulfide bonds, and residues within or surrounding the tryptophan\u2010arginine ladder. We also note the locations and potential effects of amino acid substitutions within the extracellular domains of gp130 that are associated with craniosynostosis. As focus on the physiological and pathological functions of IL\u201011 grows, the importance of high\u2010resolution structural knowledge of IL\u201011 signalling to understand disease\u2010associated mutations and to inform therapeutic strategies will only increase.<\/jats:p>","DOI":"10.1111\/febs.17307","type":"journal-article","created":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T22:30:52Z","timestamp":1730068252000},"page":"500-509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The structure of the\n                    <scp>IL<\/scp>\n                    \u201011 signalling complex provides insight into receptor variants associated with craniosynostosis"],"prefix":"10.1111","volume":"292","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2958-5698","authenticated-orcid":false,"given":"Darlene D.","family":"Sentosa","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute University of Melbourne  Parkville Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7154-780X","authenticated-orcid":false,"given":"Riley D.","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"Centre for Structural Biology, Centre for Cancer Research National Cancer Institute  Frederick MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1421-8468","authenticated-orcid":false,"given":"Natalie A.","family":"Sims","sequence":"additional","affiliation":[{"name":"St. Vincent's Institute of Medical Research  Fitzroy Australia"},{"name":"Department of Medicine at St. Vincent's Hospital The University of Melbourne  Fitzroy Australia"},{"name":"Mary Mackillop Institute for Health Research Australian Catholic University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Putoczki","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research  Parkville Australia"},{"name":"Department of Medical Biology University of Melbourne  Parkville Australia"},{"name":"Department of Surgery University of Melbourne  Parkville Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9845-7735","authenticated-orcid":false,"given":"Michael D. 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