EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers.
ジャーナル・号・ページ	Cell Res, Vol. 33, Issue 10, Page 762-774, Year 2023
掲載日	2023年6月8日
著者	Xinwei Wang / Mu Wang / Tuo Xu / Ye Feng / Qiang Shao / Shuo Han / Xiaojing Chu / Yechun Xu / Shuling Lin / Qiang Zhao / Beili Wu /
PubMed 要旨	Heterodimerization of the metabotropic glutamate receptors (mGlus) has shown importance in the functional modulation of the receptors and offers potential drug targets for treating central nervous ...Heterodimerization of the metabotropic glutamate receptors (mGlus) has shown importance in the functional modulation of the receptors and offers potential drug targets for treating central nervous system diseases. However, due to a lack of molecular details of the mGlu heterodimers, understanding of the mechanisms underlying mGlu heterodimerization and activation is limited. Here we report twelve cryo-electron microscopy (cryo-EM) structures of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers in different conformational states, including inactive, intermediate inactive, intermediate active and fully active conformations. These structures provide a full picture of conformational rearrangement of mGlu2-mGlu3 upon activation. The Venus flytrap domains undergo a sequential conformational change, while the transmembrane domains exhibit a substantial rearrangement from an inactive, symmetric dimer with diverse dimerization patterns to an active, asymmetric dimer in a conserved dimerization mode. Combined with functional data, these structures reveal that stability of the inactive conformations of the subunits and the subunit-G protein interaction pattern are determinants of asymmetric signal transduction of the heterodimers. Furthermore, a novel binding site for two mGlu4 positive allosteric modulators was observed in the asymmetric dimer interfaces of the mGlu2-mGlu4 heterodimer and mGlu4 homodimer, and may serve as a drug recognition site. These findings greatly extend our knowledge about signal transduction of the mGlus.
リンク	Cell Res / PubMed:37286794 / PubMed Central
手法	EM (単粒子)
解像度	2.8 - 3.7 Å
構造データ	36165 8jcu EMDB-36165, PDB-8jcu: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495 (dimerization mode I) 手法: EM (単粒子) / 解像度: 2.8 Å 36166 8jcv EMDB-36166, PDB-8jcv: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495 (dimerization mode II) 手法: EM (単粒子) / 解像度: 3.4 Å 36167 8jcw EMDB-36167, PDB-8jcw: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495 and NAM563 (dimerization mode I) 手法: EM (単粒子) / 解像度: 3.0 Å 36168 8jcx EMDB-36168, PDB-8jcx: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495 and NAM563 (dimerization mode II) 手法: EM (単粒子) / 解像度: 3.0 Å 36169 8jcy EMDB-36169, PDB-8jcy: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495, NAM563, and LY2389575 (dimerization mode I) 手法: EM (単粒子) / 解像度: 2.9 Å 36170 8jcz EMDB-36170, PDB-8jcz: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495, NAM563, and LY2389575 (dimerization mode III) 手法: EM (単粒子) / 解像度: 3.0 Å 36171 8jd0 EMDB-36171, PDB-8jd0: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of NAM563 手法: EM (単粒子) / 解像度: 3.3 Å 36172 8jd1 EMDB-36172, PDB-8jd1: Cryo-EM structure of mGlu2-mGlu3 heterodimer in Rco state 手法: EM (単粒子) / 解像度: 3.7 Å 36173 8jd2 EMDB-36173, PDB-8jd2: Cryo-EM structure of G protein-free mGlu2-mGlu3 heterodimer in Acc state 手法: EM (単粒子) / 解像度: 2.8 Å 36174 8jd3 EMDB-36174, PDB-8jd3: Cryo-EM structure of Gi1-bound mGlu2-mGlu3 heterodimer 手法: EM (単粒子) / 解像度: 3.3 Å 36175 8jd4 EMDB-36175, PDB-8jd4: Cryo-EM structure of G protein-free mGlu2-mGlu4 heterodimer in Acc state 手法: EM (単粒子) / 解像度: 2.9 Å 36176 8jd5 EMDB-36176, PDB-8jd5: Cryo-EM structure of Gi1-bound mGlu2-mGlu4 heterodimer 手法: EM (単粒子) / 解像度: 3.6 Å 36177 8jd6 EMDB-36177, PDB-8jd6: Cryo-EM structure of Gi1-bound metabotropic glutamate receptor mGlu4 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-36221: Cryo-EM map of Gi-bound metabotropic glutamate receptor mGlu4 focused on TMD and G protein 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-36222: Cryo-EM map of Gi1-bound metabotropic glutamate receptor mGlu4 focused on ECD 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-36226: Cryo-EM map of Gi1-bound mGlu2-mGlu4 heterodimer focused on ECD 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-36227: Cryo-EM map of Gi1-bound mGlu2-mGlu4 heterodimer focused on TMD and G protein 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-36286: The consensus Cryo-EM map of Gi1-bound mGlu2-mGlu4 heterodimer 手法: EM (単粒子) / 解像度: 3.6 Å EMDB-36287: The consensus Cryo-EM map of Gi-bound metabotropic glutamate receptor mGlu4 手法: EM (単粒子) / 解像度: 3.4 Å
化合物	ChemComp-Z99: 2-[(1S,2S)-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl)-D-alanine / LY-491395 / 抗うつ薬, アンタゴニストYM ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-CLR: CHOLESTEROL / コレステロ-ル ChemComp-J9R: 4-(1-methylpyrazol-4-yl)-7-[[(2~{S})-2-(trifluoromethyl)morpholin-4-yl]methyl]quinoline-2-carboxamide ChemComp-GLU: GLUTAMIC ACID / グルタミン酸 ChemComp-HZR: 1-butyl-3-chloranyl-4-(4-phenylpiperidin-1-yl)pyridin-2-one / 3-クロロ-1-ブチル-4-(4-フェニルピペリジノ)ピリジン-2(1H)-オン ChemComp-PEF: DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / DPPE / リン脂質YM ChemComp-BQI: 5-methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)-1,3-thiazol-2-amine / ADX-88178 ChemComp-BK0: N-(3-chlorophenyl)pyridine-2-carboxamide / N-(3-クロロフェニル)ピコリンアミド ChemComp-SEP: PHOSPHOSERINE / L-ホスホセリン
由来	homo sapiens (ヒト) escherichia coli (大腸菌)
キーワード	MEMBRANE PROTEIN / Complex structure / mGlu2-3 heterodimer / mGlu2-3 heterodimer in presence of NAM563 / mGlu2-mGlu3 heterodimer with Gi protein / mGlu2-mGlu4 heterodimer / Gi1-bound mGlu2-mGlu4 heterodimer / Gi-bound metabotropic glutamate receptor mGlu4