PDBsum entry 6w2y

Signaling protein

PDB id: 6w2y

Contents

Protein chains

663 a.a.

Ligands

NAG-NAG ×2

NAG ×4

L9Q ×2

SGG ×2

Metals

_MG ×2

PDB id:

6w2y

Name:

Signaling protein

Title:

Cryoem structure of gabab1b homodimer

Structure:

Gamma-aminobutyric acid type b receptor subunit 1. Chain: a, b. Fragment: unp residues 30-844. Synonym: gb1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: gabbr1, gprc3a. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Authors:

M.M.Papasergi-Scott,M.J.Robertson,G.Skiniotis

Key ref:

M.M.Papasergi-Scott et al. (2020). Structures of metabotropic GABA_B receptor. Nature, 584, 310-314. PubMed id: 32580208 DOI: 10.1038/s41586-020-2469-4

Date:

08-Mar-20 Release date: 01-Jul-20

Protein chains

Q9UBS5  (GABR1_HUMAN) -  Gamma-aminobutyric acid type B receptor subunit 1 from Homo sapiens

Seq: 961 a.a.

Struc: 663 a.a.

DOI no: 10.1038/s41586-020-2469-4

Nature 584:310-314 (2020)

PubMed id: 32580208

Structures of metabotropic GABA_B receptor.

M.M.Papasergi-Scott, M.J.Robertson, A.B.Seven, O.Panova, J.M.Mathiesen, G.Skiniotis.

ABSTRACT

Stimulation of the metabotropic GABA_B receptor by γ-aminobutyric acid (GABA) results in prolonged inhibition of neurotransmission, which is central to brain physiology¹. GABA_B belongs to family C of the G-protein-coupled receptors, which operate as dimers to transform synaptic neurotransmitter signals into a cellular response through the binding and activation of heterotrimeric G proteins^2,3. However, GABA_B is unique in its function as an obligate heterodimer in which agonist binding and G-protein activation take place on distinct subunits^4,5. Here we present cryo-electron microscopy structures of heterodimeric and homodimeric full-length GABA_B receptors. Complemented by cellular signalling assays and atomistic simulations, these structures reveal that extracellular loop 2 (ECL2) of GABA_B has an essential role in relaying structural transitions by ordering the linker that connects the extracellular ligand-binding domain to the transmembrane region. Furthermore, the ECL2 of each of the subunits of GABA_B caps and interacts with the hydrophilic head of a phospholipid that occupies the extracellular half of the transmembrane domain, thereby providing a potentially crucial link between ligand binding and the receptor core that engages G proteins. These results provide a starting framework through which to decipher the mechanistic modes of signal transduction mediated by GABA_B dimers, and have important implications for rational drug design that targets these receptors.