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http://purl.uniprot.org/citations/23604254http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23604254http://www.w3.org/2000/01/rdf-schema#comment"The functions of G-protein-coupled receptors (GPCRs) are primarily mediated and modulated by three families of proteins: the heterotrimeric G proteins, the G-protein-coupled receptor kinases (GRKs) and the arrestins. G proteins mediate activation of second-messenger-generating enzymes and other effectors, GRKs phosphorylate activated receptors, and arrestins subsequently bind phosphorylated receptors and cause receptor desensitization. Arrestins activated by interaction with phosphorylated receptors can also mediate G-protein-independent signalling by serving as adaptors to link receptors to numerous signalling pathways. Despite their central role in regulation and signalling of GPCRs, a structural understanding of β-arrestin activation and interaction with GPCRs is still lacking. Here we report the crystal structure of β-arrestin-1 (also called arrestin-2) in complex with a fully phosphorylated 29-amino-acid carboxy-terminal peptide derived from the human V2 vasopressin receptor (V2Rpp). This peptide has previously been shown to functionally and conformationally activate β-arrestin-1 (ref. 5). To capture this active conformation, we used a conformationally selective synthetic antibody fragment (Fab30) that recognizes the phosphopeptide-activated state of β-arrestin-1. The structure of the β-arrestin-1-V2Rpp-Fab30 complex shows marked conformational differences in β-arrestin-1 compared to its inactive conformation. These include rotation of the amino- and carboxy-terminal domains relative to each other, and a major reorientation of the 'lariat loop' implicated in maintaining the inactive state of β-arrestin-1. These results reveal, at high resolution, a receptor-interacting interface on β-arrestin, and they indicate a potentially general molecular mechanism for activation of these multifunctional signalling and regulatory proteins."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.org/dc/terms/identifier"doi:10.1038/nature12120"xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Kobilka B.K."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Manglik A."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Lefkowitz R.J."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Kossiakoff A.A."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Koide S."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Shukla A.K."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Weis W.I."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Koide A."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Tseng W.C."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Kruse A.C."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Xiao K."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Staus D.P."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Huang L.Y."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Hilger D."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Uysal S."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Paduch M."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Reis R.I."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/author"Tripathi-Shukla P."xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/name"Nature"xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/pages"137-141"xsd:string
http://purl.uniprot.org/citations/23604254http://purl.uniprot.org/core/title"Structure of active beta-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide."xsd:string
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