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- EMDB-49154: Cryo EM Structure of Full Length mGluR8 Bound to Agonist L-AP4 an... -

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Basic information

Entry
Database: EMDB / ID: EMD-49154
TitleCryo EM Structure of Full Length mGluR8 Bound to Agonist L-AP4 and PAM VU6005649, class 2
Map data
Sample
  • Complex: Metabotropic Glutamate Receptor 8 dimer
    • Protein or peptide: Metabotropic glutamate receptor 8
  • Ligand: (2S)-2-amino-4-phosphonobutanoic acid
  • Ligand: (3P,8S)-3-(2,3-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine
KeywordsGPCR / metabotropic glutamate receptor / membrane protein / synaptic protein / signaling protein
Function / homology
Function and homology information


group III metabotropic glutamate receptor activity / adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway / G protein-coupled glutamate receptor signaling pathway / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate receptor activity / regulation of synaptic transmission, glutamatergic / visual perception / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G alpha (i) signalling events / plasma membrane
Similarity search - Function
GPCR, family 3, metabotropic glutamate receptor 8 / GPCR, family 3, metabotropic glutamate receptor / : / G-protein coupled receptors family 3 signature 1. / G-protein coupled receptors family 3 signature 3. / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site ...GPCR, family 3, metabotropic glutamate receptor 8 / GPCR, family 3, metabotropic glutamate receptor / : / G-protein coupled receptors family 3 signature 1. / G-protein coupled receptors family 3 signature 3. / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site / GPCR, family 3 / G-protein coupled receptors family 3 profile. / GPCR family 3, C-terminal / 7 transmembrane sweet-taste receptor of 3 GCPR / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I
Similarity search - Domain/homology
Metabotropic glutamate receptor 8
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.97 Å
AuthorsMarx DC / Levitz JT
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)F32GM148001 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01NS129904 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)F31NS129320 United States
CitationJournal: To Be Published
Title: Structural Diversity of Metabotropic Glutamate Receptor/Beta-Arrestin Coupling
Authors: Marx DC / Gonzalez-Hernandez AJ / Huynh K / Strauss A / Rico C / Siepe D / Gallo PN / Lee J / Sharghi S / Arefin A / Broichhagen J / Eliezer D / Kalocsay M / Khelashvilli G / Levitz J
History
DepositionFeb 10, 2025-
Header (metadata) releaseSep 9, 2026-
Map releaseSep 9, 2026-
UpdateSep 9, 2026-
Current statusSep 9, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_49154.png

Downloads & links

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Map

FileDownload / File: emd_49154.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 416 pix.
= 343.2 Å		0.83 Å/pix.
x 416 pix.
= 343.2 Å		0.83 Å/pix.
x 416 pix.
= 343.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.825 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.265
Minimum - Maximum-0.64535284 - 1.3956592
Average (Standard dev.)0.00043505 (±0.028746283)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions416416416
Spacing416416416
CellA=B=C: 343.19998 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_49154_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_49154_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Metabotropic Glutamate Receptor 8 dimer

EntireName: Metabotropic Glutamate Receptor 8 dimer
Components
  • Complex: Metabotropic Glutamate Receptor 8 dimer
    • Protein or peptide: Metabotropic glutamate receptor 8
  • Ligand: (2S)-2-amino-4-phosphonobutanoic acid
  • Ligand: (3P,8S)-3-(2,3-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine

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Supramolecule #1: Metabotropic Glutamate Receptor 8 dimer

SupramoleculeName: Metabotropic Glutamate Receptor 8 dimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 260 KDa

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Macromolecule #1: Metabotropic glutamate receptor 8

MacromoleculeName: Metabotropic glutamate receptor 8 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 100.881039 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKTIIALSYI FCLVFADYKD DDDAAAQEYA HSIRVDGDII LGGLFPVHAK GERGVPCGEL KKEKGIHRLE AMLYAIDQIN KDPDLLSNI TLGVRILDTC SRDTYALEQS LTFVQALIEK DASDVKCANG DPPIFTKPDK ISGVIGAAAS SVSIMVANIL R LFKIPQIS ...String:
MKTIIALSYI FCLVFADYKD DDDAAAQEYA HSIRVDGDII LGGLFPVHAK GERGVPCGEL KKEKGIHRLE AMLYAIDQIN KDPDLLSNI TLGVRILDTC SRDTYALEQS LTFVQALIEK DASDVKCANG DPPIFTKPDK ISGVIGAAAS SVSIMVANIL R LFKIPQIS YASTAPELSD NTRYDFFSRV VPPDSYQAQA MVDIVTALGW NYVSTLASEG NYGESGVEAF TQISREIGGV CI AQSQKIP REPRPGEFEK IIKRLLETPN ARAVIMFANE DDIRRILEAA KKLNQSGHFL WIGSDSWGSK IAPVYQQEEI AEG AVTILP KRASIDGFDR YFRSRTLANN RRNVWFAEFW EENFGCKLGS HGKRNSHIKK CTGLERIARD SSYEQEGKVQ FVID AVYSM AYALHNMHKD LCPGYIGLCP RMSTIDGKEL LGYIRAVNFN GSAGTPVTFN ENGDAPGRYD IFQYQITNKS TEYKV IGHW TNQLHLKVED MQWAHREHTH PASVCSLPCK PGERKKTVKG VPCCWHCERC EGYNYQVDEL SCELCPLDQR PNMNRT GCQ LIPIIKLEWH SPWAVVPVFV AILGIIATTF VIVTFVRYND TPIVRASGRE LSYVLLTGIF LCYSITFLMI AAPDTII CS FRRVFLGLGM CFSYAALLTK TNRIHRIFEQ GKKSVTAPKF ISPASQLVIT FSLISVQLLG VFVWFVVDPP HIIIDYGE Q RTLDPEKARG VLKCDISDLS LICSLGYSIL LMVTCTVYAI KTRGVPETFN EAKPIGFTMY TTCIIWLAFI PIFFGTAQS AEKMYIQTTT LTVSMSLSAS VSLGMLYMPK VYIIIFHPEQ NVQKRKRSFK AVVTAATMQS KLIQKGNDRP NGEVKSELCE SLETNTSST KTTYISYSNH SI

UniProtKB: Metabotropic glutamate receptor 8

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Macromolecule #2: (2S)-2-amino-4-phosphonobutanoic acid

MacromoleculeName: (2S)-2-amino-4-phosphonobutanoic acid / type: ligand / ID: 2 / Number of copies: 2 / Formula: E7P
Molecular weightTheoretical: 183.1 Da
Chemical component information

ChemComp-E7P:
(2S)-2-amino-4-phosphonobutanoic acid / agonist*YM

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Macromolecule #3: (3P,8S)-3-(2,3-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluor...

MacromoleculeName: (3P,8S)-3-(2,3-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine
type: ligand / ID: 3 / Number of copies: 2 / Formula: A1BWG
Molecular weightTheoretical: 357.278 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration4.5 mg/mL
BufferpH: 7.5
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Support film - Material: GOLD / Support film - topology: HOLEY
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Average electron dose: 58.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.7000000000000001 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

8tqb

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.97 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 298102
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementSpace: REAL / Protocol: AB INITIO MODEL
Output model

PDB-9n8z:
Cryo EM Structure of Full Length mGluR8 Bound to Agonist L-AP4 and PAM VU6005649, class 2

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