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dc.contributor.authorBruell, S
dc.contributor.authorSethi, A
dc.contributor.authorSmith, N
dc.contributor.authorScott, DJ
dc.contributor.authorHossain, MA
dc.contributor.authorWu, Q-P
dc.contributor.authorGuo, Z-Y
dc.contributor.authorPetrie, EJ
dc.contributor.authorGooley, PR
dc.contributor.authorBathgate, RAD
dc.date.accessioned2020-12-18T04:27:07Z
dc.date.available2020-12-18T04:27:07Z
dc.date.issued2017-06-12
dc.identifierpii: 10.1038/s41598-017-03638-4
dc.identifier.citationBruell, S., Sethi, A., Smith, N., Scott, D. J., Hossain, M. A., Wu, Q. -P., Guo, Z. -Y., Petrie, E. J., Gooley, P. R. & Bathgate, R. A. D. (2017). Distinct activation modes of the Relaxin Family Peptide Receptor 2 in response to insulin-like peptide 3 and relaxin. SCIENTIFIC REPORTS, 7 (1), https://doi.org/10.1038/s41598-017-03638-4.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/256199
dc.description.abstractRelaxin family peptide receptor 2 (RXFP2) is a GPCR known for its role in reproductive function. It is structurally related to the human relaxin receptor RXFP1 and can be activated by human gene-2 (H2) relaxin as well as its cognate ligand insulin-like peptide 3 (INSL3). Both receptors possess an N-terminal low-density lipoprotein type a (LDLa) module that is necessary for activation and is joined to a leucine-rich repeat domain by a linker. This linker has been shown to be important for H2 relaxin binding and activation of RXFP1 and herein we investigate the role of the equivalent region of RXFP2. We demonstrate that the linker's highly-conserved N-terminal region is essential for activation of RXFP2 in response to both ligands. In contrast, the linker is necessary for H2 relaxin, but not INSL3, binding. Our results highlight the distinct mechanism by which INSL3 activates RXFP2 whereby ligand binding mediates reorientation of the LDLa module by the linker region to activate the RXFP2 transmembrane domains in conjunction with the INSL3 A-chain. In contrast, relaxin activation of RXFP2 involves a more RXFP1-like mechanism involving binding to the LDLa-linker, reorientation of the LDLa module and activation of the transmembrane domains by the LDLa alone.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleDistinct activation modes of the Relaxin Family Peptide Receptor 2 in response to insulin-like peptide 3 and relaxin
dc.typeJournal Article
dc.identifier.doi10.1038/s41598-017-03638-4
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleScientific Reports
melbourne.source.volume7
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1214946
melbourne.contributor.authorSethi, Ashish
melbourne.contributor.authorScott, Daniel
melbourne.contributor.authorHossain, Mohammed
melbourne.contributor.authorPetrie, Emma
melbourne.contributor.authorGooley, Paul
melbourne.contributor.authorBathgate, Ross
melbourne.contributor.authorBruell, Shoni
dc.identifier.eissn2045-2322
melbourne.accessrightsOpen Access


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