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-Structure paper
タイトル | Stepwise activation of a metabotropic glutamate receptor. |
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ジャーナル・号・ページ | Nature, Vol. 629, Issue 8013, Page 951-956, Year 2024 |
掲載日 | 2024年4月17日 |
著者 | Kaavya Krishna Kumar / Haoqing Wang / Chris Habrian / Naomi R Latorraca / Jun Xu / Evan S O'Brien / Chensong Zhang / Elizabeth Montabana / Antoine Koehl / Susan Marqusee / Ehud Y Isacoff / Brian K Kobilka / |
PubMed 要旨 | Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich ...Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich domain to their 7-transmembrane domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the extracellular ligand-binding domain to the G protein-coupling 7-transmembrane domain. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging, we reveal distinct receptor conformations upon allosteric modulator and G protein binding. |
リンク | Nature / PubMed:38632403 |
手法 | EM (単粒子) |
解像度 | 2.9 - 3.5 Å |
構造データ | EMDB-41069, PDB-8t6j: EMDB-41092, PDB-8t7h: EMDB-41099, PDB-8t8m: EMDB-41139, PDB-8tao: |
化合物 | ChemComp-YKU: ChemComp-QUS: |
由来 |
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キーワード | SIGNALING PROTEIN / GPCR |