Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers.
Journal, issue, pages	Cell Res, Vol. 33, Issue 10, Page 762-774, Year 2023
Publish date	Jun 8, 2023
Authors	Xinwei Wang / Mu Wang / Tuo Xu / Ye Feng / Qiang Shao / Shuo Han / Xiaojing Chu / Yechun Xu / Shuling Lin / Qiang Zhao / Beili Wu /
PubMed Abstract	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.
External links	Cell Res / PubMed:37286794 / PubMed Central
Methods	EM (single particle)
Resolution	2.8 - 3.7 Å
Structure data	36165 8jcu EMDB-36165, PDB-8jcu: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495 (dimerization mode I) Method: EM (single particle) / Resolution: 2.8 Å 36166 8jcv EMDB-36166, PDB-8jcv: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495 (dimerization mode II) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 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) Method: EM (single particle) / Resolution: 3.0 Å 36171 8jd0 EMDB-36171, PDB-8jd0: Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of NAM563 Method: EM (single particle) / Resolution: 3.3 Å 36172 8jd1 EMDB-36172, PDB-8jd1: Cryo-EM structure of mGlu2-mGlu3 heterodimer in Rco state Method: EM (single particle) / Resolution: 3.7 Å 36173 8jd2 EMDB-36173, PDB-8jd2: Cryo-EM structure of G protein-free mGlu2-mGlu3 heterodimer in Acc state Method: EM (single particle) / Resolution: 2.8 Å 36174 8jd3 EMDB-36174, PDB-8jd3: Cryo-EM structure of Gi1-bound mGlu2-mGlu3 heterodimer Method: EM (single particle) / Resolution: 3.3 Å 36175 8jd4 EMDB-36175, PDB-8jd4: Cryo-EM structure of G protein-free mGlu2-mGlu4 heterodimer in Acc state Method: EM (single particle) / Resolution: 2.9 Å 36176 8jd5 EMDB-36176, PDB-8jd5: Cryo-EM structure of Gi1-bound mGlu2-mGlu4 heterodimer Method: EM (single particle) / Resolution: 3.6 Å 36177 8jd6 EMDB-36177, PDB-8jd6: Cryo-EM structure of Gi1-bound metabotropic glutamate receptor mGlu4 Method: EM (single particle) / Resolution: 3.4 Å EMDB-36221: Cryo-EM map of Gi-bound metabotropic glutamate receptor mGlu4 focused on TMD and G protein Method: EM (single particle) / Resolution: 3.3 Å EMDB-36222: Cryo-EM map of Gi1-bound metabotropic glutamate receptor mGlu4 focused on ECD Method: EM (single particle) / Resolution: 2.9 Å EMDB-36226: Cryo-EM map of Gi1-bound mGlu2-mGlu4 heterodimer focused on ECD Method: EM (single particle) / Resolution: 2.9 Å EMDB-36227: Cryo-EM map of Gi1-bound mGlu2-mGlu4 heterodimer focused on TMD and G protein Method: EM (single particle) / Resolution: 3.4 Å EMDB-36286: The consensus Cryo-EM map of Gi1-bound mGlu2-mGlu4 heterodimer Method: EM (single particle) / Resolution: 3.6 Å EMDB-36287: The consensus Cryo-EM map of Gi-bound metabotropic glutamate receptor mGlu4 Method: EM (single particle) / Resolution: 3.4 Å
Chemicals	ChemComp-Z99: 2-[(1S,2S)-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl)-D-alanine / antidepressant, antagonistYM ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-CLR: CHOLESTEROL ChemComp-J9R: 4-(1-methylpyrazol-4-yl)-7-[[(2~{S})-2-(trifluoromethyl)morpholin-4-yl]methyl]quinoline-2-carboxamide ChemComp-GLU: GLUTAMIC ACID ChemComp-HZR: 1-butyl-3-chloranyl-4-(4-phenylpiperidin-1-yl)pyridin-2-one ChemComp-PEF: DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / phospholipidYM ChemComp-BQI: 5-methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)-1,3-thiazol-2-amine ChemComp-BK0: N-(3-chlorophenyl)pyridine-2-carboxamide ChemComp-SEP: PHOSPHOSERINE
Source	homo sapiens (human) escherichia coli (E. coli)
Keywords	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