Reagent or resource	Source	Identifier
Bacterial and virus strains
E. coli cells DH5α	NEB	C2987
E. coli cells DH10Bac	Invitrogen/ThermoFisher	10361012
Chemicals, peptides, and recombinant proteins
pFastBac vector	Invitrogen/ThermoFisher	Cat#10712024
BacMam pCMV-DEST vector	Invitrogen/ThermoFisher	A24223
pCDNA3.1 vector	Invitrogen/ThermoFisher	Cat#V79020
Tag-Lite buffer 5x	PerkinElmer/Cisbio	Cat#LABMED
SNAP-Lumi4-Tb	PerkinElmer/Cisbio	Cat#SSNPTBX
SNAP-red	PerkinElmer/Cisbio	Cat#SSNPREDF
IPOne Gq kit	PerkinElmer/Cisbio	Cat#62IPAPEC
Iodoacetamide	Sigma	Cat#I6125
Phenylmethanesulfonyl fluoride (PMSF)	Sigma	Cat#P7626
cOmplete EDTA-free inhibitor cocktail	Sigma	Cat# 5056489001
Lauryl Maltose Neopentyl (MNG)	Anatrace	Cat#NG310
n-Dodecyl-beta-D-maltopyranoside (DDM)	Anatrace	Cat#D310LA
n-Decyl-beta-D-maltopyranoside (DM)	Anatrace	Cat#D322
n-Nonyl-beta-D-Glucopyranoside (NG)	Anatrace	Cat#N324
1-O-(n-Octyl)-tetraethyleneglycol (C8E4)	Anatrace	Cat#T350
Monoolein, 9.9 MAG	Molecular dimensions	Cat#MD2-67
Cholesterol	Anatrace	Cat#CH200
Cholesterol hemisuccinate, Tris Salt (CHS)	Anatrace	Cat#CH210
HisTrap HP	GE Healthcare	Cat#17-5248-02
ANTI-FLAG® M1 Agarose Affinity Gel	Sigma-Aldrich	Cat#A4596
FLAG peptide	Covalab	https://www.covalab.com/peptide-synthesis
Superdex 200 increase 10/300 GL	GE Healthcare	Cat#28-9909-44
EX-CELL420 Serum-Free Medium	Sigma-Aldrich	Cat#14420
DMEM	Life Technologie	41965062
DMEM Glutamax	Life Technologie	31966021
Freestyle serum-Free Medium	Life Technologie	12338018
MPEP	Bio-techne	Cat#1212/10
Tritiated MPEP	Isobio	ART 1209-250 μCi
VU0424465	Nasrallah et al., 2018	N/A
LY341495 disodium salt	Bio-techne	Cat#4062/1
L-Quisqualic acid	Bio-techne	Cat#0188/10
Polyethylenimine	Polyscience Europe	Cat#02371
GTPγS	Roche	Cat#10220647001
YM-254890	Cayman Chemicals	Cat#29735
GTPase-GloTM assay	Promega	Cat#V7681
Experimental models: Cell lines
Insect cell line Sf9	Life Technologies	Cat#11496015
HEK293 human cells	ATCC	CRL-1573
HEK293T human cells	ATCC	CRL-3216
HEK293S GNTi− human cells	Reeves et al., 2002	N/A
Recombinant DNA
pBacMam-pCMV-DEST mGlu5-5M	This study	N/A
pFastBac-mGlu5-5M	This study	N/A
pFastBac-7TM-mGlu5-5M	This study	N/A
pFastBac- mGlu5-StaR(569-836)-T4L	Doré et al., 2014	N/A
pcDNA-SNAP-mGlu5	Gift from CisBio	N/A
pcDNA-SNAP-mGlu5-Δ856	This study	N/A
pcDNA-SNAP- mGlu5-5M	This study	N/A
pcDNA-SNAP- mGlu5-4M	This study	N/A
pcDNA-SNAP- mGlu5-3M	This study	N/A
pcDNA-SNAP- mGlu5-2M	This study	N/A
pcDNA-SNAP- mGlu5-1M	This study	N/A
pcDNA-SNAP-mGlu5-Δ856 single point mutants (I651A, P655A, S658A, Y659A, R668A, V740A, T742A, L744A, S753A, N747A, G748A, T777A, T781A, W785A, A787L, F788A, Y792A, G794A, I799A, M802A, S805A, V806A, S809A, A810L, A813L, A855L, A856L)	This study	N/A
Software and algorithms
PyMOL	Schrödinger	https://pymol.org/2/
Prism v.6.0	GraphPad Software	https://www.graphpad.com/scientific-software/prism/
XDS	https://xds.mr.mpg.de/	VERSION Mar 15, 2019 BUILD = 20190806
XDSCC12	https://xds.mr.mpg.de/	xdscc12 KD 2019-07-26
XSCALE	https://xds.mr.mpg.de/html_doc/xscale_program.html	VERSION Jan 31, 2020 BUILD = 20200417
CTFFIND4	Rohou and Grigorieff, 2015	CTFFIND4
Relion	https://www3.mrc-lmb.cam.ac.uk/relion/index.php/Main_Page	Relion 3.1
SerialEM	https://bio3d.colorado.edu/SerialEM/	SerialEM 3.9 beta
Coot	https://www.ccp4.ac.uk/	Coot 0.9.3
ccpem	https://www.ccp4.ac.uk/	CCPEM 1.5.0
Phenix	https://phenix-online.org/	Phenix 1.18.2-3874
Refmac	http://www.ccp4.ac.uk	Refmac 5.8.0267
Chimera	www.cgl.ucsf.edu/chimera	UCSF Chimera Version 1.13.1
Topaz	http://cb.csail.mit.edu/cb/topaz/; Bepler et al., 2019	topaz v0.2.5
Deposited data
mGlu5 −5M bound to LY341495 and MPEP	This study	EMDB-31537, PDB – 7FD9
mGlu5 −5M bound to quisqualate and VU0424465	This study	EMBD-31536, PDB – 7FD8
mGlu5 StaR(569-836)-T4L bound to alloswitch-1	This study	PDB - 7P2L
Others
Quantifoil 0.6/1 um 300 mesh Au grids	https://www.quantifoil.com	N1-C11nAu30-01