- EMDB-21685: Structure of human GABA(B) receptor in an inactive state -
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Basic information
Entry
Database: EMDB / ID: EMD-21685
Title
Structure of human GABA(B) receptor in an inactive state
Map data
Final composite map combining local reconstructions for the extracellular and transmembrane domains. Map was re-sampled in Chimera with pixel spacing 1.1 angstrom.
Sample
Complex: Heterodimer human GABA(B) receptor composed of GABA(B1b) and GABA(B2) subunits.
Protein or peptide: Gamma-aminobutyric acid type B receptor subunit 1
Protein or peptide: Gamma-aminobutyric acid type B receptor subunit 2
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM088454
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
U2CES030158
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM125801
United States
National Institutes of Health/Office of the Director
R01GM107462
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P41GM116799
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P41GM103310
United States
Citation
Journal: Nature / Year: 2020 Title: Structure of human GABA receptor in an inactive state. Authors: Jinseo Park / Ziao Fu / Aurel Frangaj / Jonathan Liu / Lidia Mosyak / Tong Shen / Vesna N Slavkovich / Kimberly M Ray / Jaume Taura / Baohua Cao / Yong Geng / Hao Zuo / Yongjun Kou / Robert ...Authors: Jinseo Park / Ziao Fu / Aurel Frangaj / Jonathan Liu / Lidia Mosyak / Tong Shen / Vesna N Slavkovich / Kimberly M Ray / Jaume Taura / Baohua Cao / Yong Geng / Hao Zuo / Yongjun Kou / Robert Grassucci / Shaoxia Chen / Zheng Liu / Xin Lin / Justin P Williams / William J Rice / Edward T Eng / Rick K Huang / Rajesh K Soni / Brian Kloss / Zhiheng Yu / Jonathan A Javitch / Wayne A Hendrickson / Paul A Slesinger / Matthias Quick / Joseph Graziano / Hongtao Yu / Oliver Fiehn / Oliver B Clarke / Joachim Frank / Qing R Fan / Abstract: The human GABA receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction. A unique ...The human GABA receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction. A unique GPCR that is known to require heterodimerization for function, the GABA receptor has two subunits, GABA and GABA, that are structurally homologous but perform distinct and complementary functions. GABA recognizes orthosteric ligands, while GABA couples with G proteins. Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail. Although the VFT heterodimer structure has been resolved, the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABA receptor, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique 'intersubunit latch' within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.
History
Deposition
Apr 10, 2020
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Header (metadata) release
Jul 1, 2020
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Map release
Jul 1, 2020
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Update
Aug 26, 2020
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Current status
Aug 26, 2020
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
EMPIAR-10410 (Title: Structure of human GABA(B) receptor in an inactive state Data size: 854.1 Data #1: Unaligned multi-frame micrographs of GABA(B) receptor in the inactive state [micrographs - multiframe])
Download / File: emd_21685.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotation
Final composite map combining local reconstructions for the extracellular and transmembrane domains. Map was re-sampled in Chimera with pixel spacing 1.1 angstrom.
Voxel size
X=Y=Z: 1.1 Å
Density
Contour Level
By AUTHOR: 0.5 / Movie #1: 0.6
Minimum - Maximum
-0.29351062 - 5.1695056
Average (Standard dev.)
0.017307602 (±0.080392115)
Symmetry
Space group: 1
Details
EMDB XML:
Map geometry
Axis order
X
Y
Z
Origin
0
0
0
Dimensions
256
256
256
Spacing
256
256
256
Cell
A=B=C: 281.6 Å α=β=γ: 90.0 °
CCP4 map header:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.1
1.1
1.1
M x/y/z
256
256
256
origin x/y/z
0.000
0.000
0.000
length x/y/z
281.600
281.600
281.600
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
0
0
0
NX/NY/NZ
360
360
360
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
256
256
256
D min/max/mean
-0.294
5.170
0.017
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Supplemental data
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Additional map: Local reconstruction for the extracellular domain. Map was...
Details: Solutions were made fresh from concentrated and filtered to avoid microbial contamination.
Grid
Model: Quantifoil R0.6/1 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 50.0 nm / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Atmosphere: OTHER
Vitrification
Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: blot for 4 seconds before plunging.
Details
This sample was monodisperse
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Electron microscopy
Microscope
FEI TITAN KRIOS
Temperature
Max: 100.0 K
Specialist optics
Energy filter - Slit width: 20 eV
Details
Preliminary grid screening was performed manually.
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 1-60 / Number grids imaged: 1 / Number real images: 3435 / Average exposure time: 12.0 sec. / Average electron dose: 85.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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