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TitleStructure of the class C orphan GPCR GPR158 in complex with RGS7-Gβ5.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 6805, Year 2021
Publish dateNov 23, 2021
AuthorsEunyoung Jeong / Yoojoong Kim / Jihong Jeong / Yunje Cho /
PubMed AbstractGPR158, a class C orphan GPCR, functions in cognition, stress-induced mood control, and synaptic development. Among class C GPCRs, GPR158 is unique as it lacks a Venus flytrap-fold ligand-binding ...GPR158, a class C orphan GPCR, functions in cognition, stress-induced mood control, and synaptic development. Among class C GPCRs, GPR158 is unique as it lacks a Venus flytrap-fold ligand-binding domain and terminates Gαi/o protein signaling through the RGS7-Gβ5 heterodimer. Here, we report the cryo-EM structures of GPR158 alone and in complex with one or two RGS7-Gβ5 heterodimers. GPR158 dimerizes through Per-Arnt-Sim-fold extracellular and transmembrane (TM) domains connected by an epidermal growth factor-like linker. The TM domain (TMD) reflects both inactive and active states of other class C GPCRs: a compact intracellular TMD, conformations of the two intracellular loops (ICLs) and the TMD interface formed by TM4/5. The ICL2, ICL3, TM3, and first helix of the cytoplasmic coiled-coil provide a platform for the DHEX domain of one RGS7 and the second helix recruits another RGS7. The unique features of the RGS7-binding site underlie the selectivity of GPR158 for RGS7.
External linksNat Commun / PubMed:34815401 / PubMed Central
MethodsEM (single particle)
Resolution3.52 - 4.7 Å
Structure data

EMDB-31351, PDB-7ewl:
cryo-EM structure of apo GPR158
Method: EM (single particle) / Resolution: 3.52 Å

EMDB-31360, PDB-7ewp:
Cryo-EM structure of human GPR158 in complex with RGS7-Gbeta5 in a 2:1:1 ratio
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-31363, PDB-7ewr:
Cryo-EM structure of human GPR158 in complex with RGS7-Gbeta5 in a 2:2:2 ratio
Method: EM (single particle) / Resolution: 4.7 Å

EMDB-31365:
Locally refined cryo-EM map of GPR158 in complex with RGS7-Gbeta5 in a 2:1:1 ratio
Method: EM (single particle) / Resolution: 3.95 Å

EMDB-31366:
Locally refined cryo-EM map of GPR158 in complex with RGS7-Gbeta5 in a 2:2:2 ratio
Method: EM (single particle) / Resolution: 4.65 Å

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / Class C orphan GPCR / depression / neuronal signaling / PAS-folded GPCR / noncanonical signaling GPCR / GPCR

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