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-Structure paper
| タイトル | Molecular basis of β-arrestin coupling to the metabotropic glutamate receptor mGlu3. |
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| ジャーナル・号・ページ | Nat Chem Biol, Vol. 21, Issue 8, Page 1262-1269, Year 2025 |
| 掲載日 | 2025年3月6日 |
著者 | Tianlei Wen / Mei Du / Yue Lu / Nan Jia / Xuhang Lu / Ning Liu / Shenghai Chang / Xing Zhang / Yuequan Shen / Xue Yang / ![]() |
| PubMed 要旨 | β-Arrestins (βarrs) mediate the desensitization and internalization of activated G-protein-coupled receptors (GPCRs). The molecular mechanism by which dimeric family C GPCR members recruit ...β-Arrestins (βarrs) mediate the desensitization and internalization of activated G-protein-coupled receptors (GPCRs). The molecular mechanism by which dimeric family C GPCR members recruit arrestins remains elusive. Here we report two structures of metabotropic glutamate receptor subtype 3 (mGlu3) coupled to βarr1, with stoichiometries of 2:1 and 2:2. The L-glutamate-bound mGlu3 dimer adopts an inactive state, with both Venus flytrap domains closed, engaging βarr1 either asymmetrically or symmetrically. The transmembrane domain of the mGlu3 protomer interacts with βarr1 through a binding pocket formed by three intracellular loops and an ordered C-terminal region. Three phosphorylation sites (pS857, pS859 and pT860) on the C-terminal tail of mGlu3 engage the N domain of βarr1. βarr1 stabilizes mGlu3 in an inactive conformation, characterized by a TM3/TM4-TM3/TM4 dimeric interface, previously observed in the negative allosteric modulator-bound structure of mGlu3. Our findings provide important insights into βarr-mediated inactivation of family C GPCRs. |
リンク | Nat Chem Biol / PubMed:40050438 |
| 手法 | EM (単粒子) |
| 解像度 | 3.6 - 3.9 Å |
| 構造データ | EMDB-60588, PDB-9ii2: EMDB-60589, PDB-9ii3: ![]() EMDB-60942: Focused map of mGlu3 and beta-arrestin1 2:2 Compex ECD domain (PDB 9II2) |
| 化合物 | ![]() ChemComp-GLU: ![]() ChemComp-CLR: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / complex |
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