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dc.contributor.authorXu, Y
dc.contributor.authorKong, GK-W
dc.contributor.authorMenting, JG
dc.contributor.authorMargetts, MB
dc.contributor.authorDelaine, CA
dc.contributor.authorJenkin, LM
dc.contributor.authorKiselyov, VV
dc.contributor.authorDe Meyts, P
dc.contributor.authorForbes, BE
dc.contributor.authorLawrence, MC
dc.date.accessioned2020-12-18T04:31:16Z
dc.date.available2020-12-18T04:31:16Z
dc.date.issued2018-02-26
dc.identifierpii: 10.1038/s41467-018-03219-7
dc.identifier.citationXu, Y., Kong, G. K. -W., Menting, J. G., Margetts, M. B., Delaine, C. A., Jenkin, L. M., Kiselyov, V. V., De Meyts, P., Forbes, B. E. & Lawrence, M. C. (2018). How ligand binds to the type 1 insulin-like growth factor receptor. NATURE COMMUNICATIONS, 9 (1), https://doi.org/10.1038/s41467-018-03219-7.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/256230
dc.description.abstractHuman type 1 insulin-like growth factor receptor is a homodimeric receptor tyrosine kinase that signals into pathways directing normal cellular growth, differentiation and proliferation, with aberrant signalling implicated in cancer. Insulin-like growth factor binding is understood to relax conformational restraints within the homodimer, initiating transphosphorylation of the tyrosine kinase domains. However, no three-dimensional structures exist for the receptor ectodomain to inform atomic-level understanding of these events. Here, we present crystal structures of the ectodomain in apo form and in complex with insulin-like growth factor I, the latter obtained by crystal soaking. These structures not only provide a wealth of detail of the growth factor interaction with the receptor's primary ligand-binding site but also indicate that ligand binding separates receptor domains by a mechanism of induced fit. Our findings are of importance to the design of agents targeting IGF-1R and its partner protein, the human insulin receptor.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleHow ligand binds to the type 1 insulin-like growth factor receptor
dc.typeJournal Article
dc.identifier.doi10.1038/s41467-018-03219-7
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleNature Communications
melbourne.source.volume9
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1317548
melbourne.contributor.authorLawrence, Michael
melbourne.contributor.authorXu, Yibin
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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