PDBsum entry 6n4x

Membrane protein

PDB id: 6n4x

Contents

Protein chains

506 a.a.

Ligands

NAG ×6

Metals

_MG

PDB id:

6n4x

Name:

Membrane protein

Title:

Metabotropic glutamate receptor 5 apo form ligand binding domain

Structure:

Metabotropic glutamate receptor 5. Chain: a, b. Synonym: mglur5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: grm5, gprc1e, mglur5. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Expression_system_atcc_number: crl-1711.

Resolution:

4.00Å R-factor: 0.271 R-free: 0.282

Authors:

A.Koehl,H.Hu,D.Feng,B.Sun,W.I.Weis,G.S.Skiniotis,J.M.Mathiesen, B.K.Kobilka

Key ref:

A.Koehl et al. (2019). Structural insights into the activation of metabotropic glutamate receptors. Nature, 566, 79-84. PubMed id: 30675062 DOI: 10.1038/s41586-019-0881-4

Date:

20-Nov-18 Release date: 23-Jan-19

Protein chains

P41594  (GRM5_HUMAN) -  Metabotropic glutamate receptor 5 from Homo sapiens

Seq: 1212 a.a.

Struc: 506 a.a.

DOI no: 10.1038/s41586-019-0881-4

Nature 566:79-84 (2019)

PubMed id: 30675062

Structural insights into the activation of metabotropic glutamate receptors.

A.Koehl, H.Hu, D.Feng, B.Sun, Y.Zhang, M.J.Robertson, M.Chu, T.S.Kobilka, T.Laermans, J.Steyaert, J.Tarrasch, S.Dutta, R.Fonseca, W.I.Weis, J.M.Mathiesen, G.Skiniotis, B.K.Kobilka.

ABSTRACT

Metabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich domains to their 7-transmembrane domains. Spectroscopic studies show that signalling is a dynamic process, in which large-scale conformational changes underlie the transmission of signals from the extracellular Venus flytraps to the G protein-coupling domains-the 7-transmembrane domains-in the membrane. Here, using a combination of X-ray crystallography, cryo-electron microscopy and signalling studies, we present a structural framework for the activation mechanism of metabotropic glutamate receptor subtype 5. Our results show that agonist binding at the Venus flytraps leads to a compaction of the intersubunit dimer interface, thereby bringing the cysteine-rich domains into close proximity. Interactions between the cysteine-rich domains and the second extracellular loops of the receptor enable the rigid-body repositioning of the 7-transmembrane domains, which come into contact with each other to initiate signalling.