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TitleStructural basis of GABA receptor-G protein coupling.
Journal, issue, pagesNature, Vol. 594, Issue 7864, Page 594-598, Year 2021
Publish dateApr 28, 2021
AuthorsCangsong Shen / Chunyou Mao / Chanjuan Xu / Nan Jin / Huibing Zhang / Dan-Dan Shen / Qingya Shen / Xiaomei Wang / Tingjun Hou / Zhong Chen / Philippe Rondard / Jean-Philippe Pin / Yan Zhang / Jianfeng Liu /
PubMed AbstractG-protein-coupled receptors (GPCRs) have central roles in intercellular communication. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is ...G-protein-coupled receptors (GPCRs) have central roles in intercellular communication. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure of the class-C heterodimeric GABA receptor, which is activated by the inhibitory transmitter GABA, in its active form complexed with G protein. We found that a single G protein interacts with the GB2 subunit of the GABA receptor at a site that mainly involves intracellular loop 2 on the side of the transmembrane domain. This is in contrast to the G protein binding in a central cavity, as has been observed with other classes of GPCR. This binding mode results from the active form of the transmembrane domain of this GABA receptor being different from that of other GPCRs, as it shows no outside movement of transmembrane helix 6. Our work also provides details of the inter- and intra-subunit changes that link agonist binding to G-protein activation in this heterodimeric complex.
External linksNature / PubMed:33911284 / PubMed Central
MethodsEM (single particle)
Resolution3.5 Å
Structure data

31049

7eb2

EMDB-31049, PDB-7eb2:
Cryo-EM structure of human GABA(B) receptor-Gi protein complex
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-2C0:
baclofen / medication*YM / Baclofen

ChemComp-FN0:
(3S)-5,7-ditert-butyl-3-oxidanyl-3-(trifluoromethyl)-1-benzofuran-2-one

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsMEMBRANE PROTEIN / GABAB / Cryo-EM / GPCR / Gi

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