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- EMDB-39345: Cryo-EM structure of human apo GPR156 -

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Basic information

Entry
Database: EMDB / ID: EMD-39345
TitleCryo-EM structure of human apo GPR156
Map data
Sample
  • Organelle or cellular component: GPR156
    • Protein or peptide: Probable G-protein coupled receptor 156
  • Ligand: (21R,24R,27S)-24,27,28-trihydroxy-18,24-dioxo-19,23,25-trioxa-24lambda~5~-phosphaoctacosan-21-yl (9Z)-octadec-9-enoate
  • Ligand: CHOLESTEROL
KeywordsGPCR / class C / GPR156 / cryo-EM / homodimer / MEMBRANE PROTEIN
Function / homology
Function and homology information


stereocilium bundle organization / G protein-coupled GABA receptor activity / G protein-coupled receptor heterodimeric complex / gamma-aminobutyric acid signaling pathway / plasma membrane
Similarity search - Function
GPR156, 7TM domain / GPCR family 3, GABA-B receptor / G-protein coupled receptors family 3 profile. / GPCR family 3, C-terminal / 7 transmembrane sweet-taste receptor of 3 GCPR
Similarity search - Domain/homology
Probable G-protein coupled receptor 156
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.09 Å
AuthorsMa XY / Chen LN / Liao MH / Zhang LY / Xi K / Guo JM
Funding support China, 1 items
OrganizationGrant numberCountry
Not funded China
CitationJournal: Nat Commun / Year: 2024
Title: Molecular insights into the activation mechanism of GPR156 in maintaining auditory function.
Authors: Xiangyu Ma / Li-Nan Chen / Menghui Liao / Liyan Zhang / Kun Xi / Jiamin Guo / Cangsong Shen / Dan-Dan Shen / Pengjun Cai / Qingya Shen / Jieyu Qi / Huibing Zhang / Shao-Kun Zang / Ying-Jun ...Authors: Xiangyu Ma / Li-Nan Chen / Menghui Liao / Liyan Zhang / Kun Xi / Jiamin Guo / Cangsong Shen / Dan-Dan Shen / Pengjun Cai / Qingya Shen / Jieyu Qi / Huibing Zhang / Shao-Kun Zang / Ying-Jun Dong / Luwei Miao / Jiao Qin / Su-Yu Ji / Yue Li / Jianfeng Liu / Chunyou Mao / Yan Zhang / Renjie Chai /
Abstract: The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through G. Here, we firstly demonstrate that GPR156 ...The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through G. Here, we firstly demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and further reveal the structural basis of the sustained role of GPR156. We present the cryo-EM structures of human apo GPR156 and the GPR156-G complex, unveiling a small extracellular region formed by extracellular loop 2 (ECL2) and the N-terminus. The GPR156 dimer in both apo state and G protein-coupled state adopt a transmembrane (TM)5/6-TM5/6 interface, indicating the high constitutive activity of GPR156 in the apo state. Furthermore, C-terminus in G-bound subunit of GPR156 plays a dual role in promoting G protein binding within G-bound subunit while preventing the G-free subunit from binding to additional G protein. Together, these results explain how GPR156 constitutive activity is maintained through dimerization and provide a mechanistic insight into the sustained role of GPR156 in maintaining auditory function.
History
DepositionMar 2, 2024-
Header (metadata) releaseFeb 5, 2025-
Map releaseFeb 5, 2025-
UpdateFeb 5, 2025-
Current statusFeb 5, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_39345.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.93 Å/pix.
x 256 pix.
= 238.08 Å
0.93 Å/pix.
x 256 pix.
= 238.08 Å
0.93 Å/pix.
x 256 pix.
= 238.08 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.93 Å
Density
Contour LevelBy AUTHOR: 0.13
Minimum - Maximum-0.0018019152 - 1.8756349
Average (Standard dev.)0.0007221466 (±0.018985532)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 238.08 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_39345_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_39345_half_map_2.map
Projections & Slices
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Density Histograms

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Sample components

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Entire : GPR156

EntireName: GPR156
Components
  • Organelle or cellular component: GPR156
    • Protein or peptide: Probable G-protein coupled receptor 156
  • Ligand: (21R,24R,27S)-24,27,28-trihydroxy-18,24-dioxo-19,23,25-trioxa-24lambda~5~-phosphaoctacosan-21-yl (9Z)-octadec-9-enoate
  • Ligand: CHOLESTEROL

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Supramolecule #1: GPR156

SupramoleculeName: GPR156 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Probable G-protein coupled receptor 156

MacromoleculeName: Probable G-protein coupled receptor 156 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 38.47223 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MEPEINCSEL CDSFPGQELD RRPLHDLCKT TITSSHHSSK TISSLSPVLL GIVWTFLSCG LLLILFFLAF TIHCRKNRIV KMSSPNLNI VTLLGSCLTY SSAYLFGIQD VLVGSSMETL IQTRLSMLCI GTSLVFGPIL GKSWRLYKVF TQRVPDKRVI I KDLQLLGL ...String:
MEPEINCSEL CDSFPGQELD RRPLHDLCKT TITSSHHSSK TISSLSPVLL GIVWTFLSCG LLLILFFLAF TIHCRKNRIV KMSSPNLNI VTLLGSCLTY SSAYLFGIQD VLVGSSMETL IQTRLSMLCI GTSLVFGPIL GKSWRLYKVF TQRVPDKRVI I KDLQLLGL VAALLMADVI LLMTWVLTDP IQCLQILSVS MTVTGKDVSC TSTSTHFCAS RYSDVWIALI WGCKGLLLLY GA YLAGLTG HVSSPPVNQS LTIMVGVNLL VLAAGLLFVV TRYLHSWPNL VFGLTSGGIF VCTTTINCFI FIPQLKQWKA FEE ENQTIR RMAKYFSTPN KSFHTQYGEE

UniProtKB: Probable G-protein coupled receptor 156

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Macromolecule #2: (21R,24R,27S)-24,27,28-trihydroxy-18,24-dioxo-19,23,25-trioxa-24l...

MacromoleculeName: (21R,24R,27S)-24,27,28-trihydroxy-18,24-dioxo-19,23,25-trioxa-24lambda~5~-phosphaoctacosan-21-yl (9Z)-octadec-9-enoate
type: ligand / ID: 2 / Number of copies: 4 / Formula: MW9
Molecular weightTheoretical: 777.06 Da
Chemical component information

ChemComp-MW9:
(21R,24R,27S)-24,27,28-trihydroxy-18,24-dioxo-19,23,25-trioxa-24lambda~5~-phosphaoctacosan-21-yl (9Z)-octadec-9-enoate

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Macromolecule #3: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 3 / Number of copies: 9 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

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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

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 52.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 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

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.09 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 164823
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD

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