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| http://purl.uniprot.org/citations/33536342 | http://www.w3.org/2000/01/rdf-schema#comment | "Cooperative ligand binding is an important phenomenon in biological systems where ligand binding influences the binding of another ligand at an alternative site of the protein via an intramolecular network of interactions. The underlying mechanisms behind cooperative binding remain poorly understood, primarily due to the lack of structural data of these ternary complexes. Using time-resolved fluorescence resonance energy transfer (TR-FRET) studies, we show that cooperative ligand binding occurs for RORγt, a nuclear receptor associated with the pathogenesis of autoimmune diseases. To provide the crucial structural insights, we solved 12 crystal structures of RORγt simultaneously bound to various orthosteric and allosteric ligands. The presence of the orthosteric ligand induces a clamping motion of the allosteric pocket via helices 4 to 5. Additional molecular dynamics simulations revealed the unusual mechanism behind this clamping motion, with Ala355 shifting between helix 4 and 5. The orthosteric RORγt agonists regulate the conformation of Ala355, thereby stabilizing the conformation of the allosteric pocket and cooperatively enhancing the affinity of the allosteric inverse agonists."xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2021287118"xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/author | "Brunsveld L."xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/author | "Doveston R.G."xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/author | "Meijer F.A."xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/author | "de Vries R.M.J.M."xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/author | "Leijten-van de Gevel I.A."xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/pages | "e2021287118"xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/title | "Cooperativity between the orthosteric and allosteric ligand binding sites of RORgammat."xsd:string |
| http://purl.uniprot.org/citations/33536342 | http://purl.uniprot.org/core/volume | "118"xsd:string |
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