7EB2

Cryo-EM structure of human GABA(B) receptor-Gi protein complex

Summary for 7EB2

• Entry DOI: 10.2210/pdb7eb2/pdb
• EMDB information: 31049
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (8 entities in total)
• Functional Keywords: gabab, cryo-em, gpcr, gi, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 314386.07

Authors

Shen, C.,Mao, C.,Xu, C.,Jin, N.,Zhang, H.,Shen, D.,Shen, Q.,Wang, X.,Hou, T.,Rondard, P.,Chen, Z.,Pin, J.,Zhang, Y.,Liu, J. (deposition date: 2021-03-08, release date: 2021-05-05, Last modification date: 2024-10-23)

Primary citation

Shen, C.,Mao, C.,Xu, C.,Jin, N.,Zhang, H.,Shen, D.D.,Shen, Q.,Wang, X.,Hou, T.,Chen, Z.,Rondard, P.,Pin, J.P.,Zhang, Y.,Liu, J.
Structural basis of GABA B receptor-G i protein coupling.
Nature, 594:594-598, 2021

PubMed Abstract: 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.

PubMed: 33911284
DOI: 10.1038/s41586-021-03507-1

Experimental method

ELECTRON MICROSCOPY (3.5 Å)