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dc.contributor.authorBauknecht, P
dc.contributor.authorJékely, G
dc.date.accessioned2018-05-14T13:35:45Z
dc.date.issued2015-07-28
dc.description.abstractNeuropeptides, representing the largest class of neuromodulators, commonly signal by G-protein-coupled receptors (GPCRs). While the neuropeptide repertoire of several metazoans has been characterized, many GPCRs are orphans. Here, we develop a strategy to identify GPCR-peptide pairs using combinatorial screening with complex peptide mixtures. We screened 126 neuropeptides against 87 GPCRs of the annelid Platynereis and identified ligands for 19 receptors. We assigned many GPCRs to known families and identified conserved families of achatin, FMRFamide, RGWamide, FLamide, and elevenin receptors. We also identified a ligand for the Platynereis ortholog of vertebrate thyrotropin-releasing hormone (TRH) receptors, revealing the ancient origin of TRH-receptor signaling. We predicted ligands for several metazoan GPCRs and tested predicted achatin receptors. These receptors were specifically activated by an achatin D-peptide, revealing a conserved mode of activation. Our work establishes an important resource and provides information about the complexity of peptidergic signaling in the urbilaterian.en_GB
dc.description.sponsorshipon assays. We also thank Elizabeth Williams for comments on the manuscript. The research leading to these results received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ European Research Council Grant Agreement 260821. P.B. is supported by the International Max Planck Research School (IMPRS) ‘‘From Molecules to Organismsen_GB
dc.identifier.citationVol. 12, pp. 684 - 693en_GB
dc.identifier.doi10.1016/j.celrep.2015.06.052
dc.identifier.urihttp://hdl.handle.net/10871/32841
dc.language.isoenen_GB
dc.publisherElsevieren_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/26190115en_GB
dc.rightsThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en_GB
dc.subjectAmino Acid Sequenceen_GB
dc.subjectAnimalsen_GB
dc.subjectAplysiaen_GB
dc.subjectBinding Sitesen_GB
dc.subjectCHO Cellsen_GB
dc.subjectCricetinaeen_GB
dc.subjectCricetulusen_GB
dc.subjectMolecular Docking Simulationen_GB
dc.subjectMolecular Sequence Dataen_GB
dc.subjectNeuropeptidesen_GB
dc.subjectPolychaetaen_GB
dc.subjectProtein Bindingen_GB
dc.subjectReceptors, G-Protein-Coupleden_GB
dc.subjectReceptors, Thyrotropinen_GB
dc.titleLarge-scale combinatorial deorphanization of Platynereis neuropeptide GPCRs.en_GB
dc.typeArticleen_GB
dc.date.available2018-05-14T13:35:45Z
dc.identifier.issn2211-1247,
exeter.place-of-publicationUnited Statesen_GB
dc.descriptionThis is the final version of the article. Available from the publisher via the DOI in this record.en_GB
dc.identifier.journalCell Reportsen_GB


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