[English] 日本語
Yorodumi
- EMDB-27555: Cryo-EM structure of human Glycine Receptor alpha1-beta heteromer... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-27555
TitleCryo-EM structure of human Glycine Receptor alpha1-beta heteromer, glycine-bound state1(open state)
Map data
Sample
  • Complex: heteromeric glycine receptor subunit alpha-1 and beta, glycine-bound state1 (open state)
    • Protein or peptide: x 2 types
  • Ligand: x 9 types
Keywordsglycine receptor subunit alpha-1 / glycine receptor subunit beta / Green fluorescent protein / MEMBRANE PROTEIN
Function / homology
Function and homology information


taurine binding / glycine-gated chloride channel complex / negative regulation of transmission of nerve impulse / Neurotransmitter receptors and postsynaptic signal transmission / acrosome reaction / positive regulation of acrosome reaction / synaptic transmission, glycinergic / gamma-aminobutyric acid receptor clustering / postsynaptic specialization / neuromuscular process controlling posture ...taurine binding / glycine-gated chloride channel complex / negative regulation of transmission of nerve impulse / Neurotransmitter receptors and postsynaptic signal transmission / acrosome reaction / positive regulation of acrosome reaction / synaptic transmission, glycinergic / gamma-aminobutyric acid receptor clustering / postsynaptic specialization / neuromuscular process controlling posture / extracellularly glycine-gated ion channel activity / inhibitory synapse / regulation of respiratory gaseous exchange by nervous system process / righting reflex / extracellularly glycine-gated chloride channel activity / response to alcohol / glycinergic synapse / inhibitory postsynaptic potential / cellular response to ethanol / chloride transport / adult walking behavior / cellular response to zinc ion / neurotransmitter receptor activity / glycine binding / startle response / chloride channel complex / neuronal action potential / neuropeptide signaling pathway / transmembrane transporter complex / GABA-ergic synapse / monoatomic ion transport / chloride transmembrane transport / muscle contraction / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / visual perception / bioluminescence / regulation of membrane potential / generation of precursor metabolites and energy / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / cellular response to amino acid stimulus / transmembrane signaling receptor activity / nervous system development / chemical synaptic transmission / perikaryon / postsynaptic membrane / neuron projection / external side of plasma membrane / intracellular membrane-bounded organelle / neuronal cell body / dendrite / synapse / protein-containing complex binding / zinc ion binding / identical protein binding / membrane / plasma membrane / cytoplasm
Similarity search - Function
: / Glycine receptor beta / : / Glycine receptor alpha1 / Glycine receptor alpha / Gamma-aminobutyric acid A receptor/Glycine receptor alpha / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region ...: / Glycine receptor beta / : / Glycine receptor alpha1 / Glycine receptor alpha / Gamma-aminobutyric acid A receptor/Glycine receptor alpha / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region / Neurotransmitter-gated ion-channel transmembrane domain superfamily / Neuronal acetylcholine receptor / Neurotransmitter-gated ion-channel / Neurotransmitter-gated ion-channel ligand-binding domain / Neurotransmitter-gated ion-channel ligand-binding domain superfamily / Neurotransmitter-gated ion-channel ligand binding domain / Green fluorescent protein, GFP / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein
Similarity search - Domain/homology
Glycine receptor beta / Glycine receptor subunit alpha-1 / Green fluorescent protein / Glycine receptor subunit beta
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.63 Å
AuthorsLiu X / Wang W
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)1R35GM146860 United States
CitationJournal: Nat Commun / Year: 2023
Title: Asymmetric gating of a human hetero-pentameric glycine receptor.
Authors: Xiaofen Liu / Weiwei Wang /
Abstract: Hetero-pentameric Cys-loop receptors constitute a major type of neurotransmitter receptors that enable signal transmission and processing in the nervous system. Despite intense investigations into ...Hetero-pentameric Cys-loop receptors constitute a major type of neurotransmitter receptors that enable signal transmission and processing in the nervous system. Despite intense investigations into their working mechanism and pharmaceutical potentials, how neurotransmitters activate these receptors remains unclear due to the lack of high-resolution structural information in the activated open state. Here we report near-atomic resolution structures resolved in digitonin consistent with all principle functional states of the human α1β GlyR, which is a major Cys-loop receptor that mediates inhibitory neurotransmission in the central nervous system of adults. Glycine binding induces cooperative and symmetric structural rearrangements in the neurotransmitter-binding extracellular domain but asymmetrical pore dilation in the transmembrane domain. Symmetric response in the extracellular domain is consistent with electrophysiological data showing cooperative glycine activation and contribution from both α1 and β subunits. A set of functionally essential but differentially charged amino acid residues in the transmembrane domain of the α1 and β subunits explains asymmetric activation. These findings provide a foundation for understanding how the gating of the Cys-loop receptor family members diverges to accommodate specific physiological environments.
History
DepositionJul 10, 2022-
Header (metadata) releaseOct 11, 2023-
Map releaseOct 11, 2023-
UpdateOct 30, 2024-
Current statusOct 30, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_27555.png

Downloads & links

-
Map

FileDownload / File: emd_27555.map.gz / Format: CCP4 / Size: 91.1 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 288 pix.
= 239.04 Å		0.83 Å/pix.
x 288 pix.
= 239.04 Å		0.83 Å/pix.
x 288 pix.
= 239.04 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.26
Minimum - Maximum-2.146404 - 2.76601
Average (Standard dev.)0.009411191 (±0.092162214)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 239.04 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_27555_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_27555_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

+
Entire : heteromeric glycine receptor subunit alpha-1 and beta, glycine-bo...

EntireName: heteromeric glycine receptor subunit alpha-1 and beta, glycine-bound state1 (open state)
Components
  • Complex: heteromeric glycine receptor subunit alpha-1 and beta, glycine-bound state1 (open state)
    • Protein or peptide: Glycine receptor subunit alpha-1
    • Protein or peptide: Glycine receptor subunit beta,Green fluorescent protein,Glycine receptor beta
  • Ligand: GLYCINE
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: nonane
  • Ligand: HEPTANE
  • Ligand: HEXANE
  • Ligand: UNDECANE
  • Ligand: N-BUTANE
  • Ligand: DECANE
  • Ligand: N-OCTANE

+
Supramolecule #1: heteromeric glycine receptor subunit alpha-1 and beta, glycine-bo...

SupramoleculeName: heteromeric glycine receptor subunit alpha-1 and beta, glycine-bound state1 (open state)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 240 KDa

+
Macromolecule #1: Glycine receptor subunit alpha-1

MacromoleculeName: Glycine receptor subunit alpha-1 / type: protein_or_peptide / ID: 1
Details: Derived by substitution of M3/M4 loop (residues R316-P381) s by GSSG peptide.
Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 42.421113 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ARSAPKPMSP SDFLDKLMGR TSGYDARIRP NFKGPPVNVS CNIFINSFGS IAETTMDYRV NIFLRQQWND PRLAYNEYPD DSLDLDPSM LDSIWKPDLF FANEKGAHFH EITTDNKLLR ISRNGNVLYS IRITLTLACP MDLKNFPMDV QTCIMQLESF G YTMNDLIF ...String:
ARSAPKPMSP SDFLDKLMGR TSGYDARIRP NFKGPPVNVS CNIFINSFGS IAETTMDYRV NIFLRQQWND PRLAYNEYPD DSLDLDPSM LDSIWKPDLF FANEKGAHFH EITTDNKLLR ISRNGNVLYS IRITLTLACP MDLKNFPMDV QTCIMQLESF G YTMNDLIF EWQEQGAVQV ADGLTLPQFI LKEEKDLRYC TKHYNTGKFT CIEARFHLER QMGYYLIQMY IPSLLIVILS WI SFWINMD AAPARVGLGI TTVLTMTTQS SGSRASLPKV SYVKAIDIWM AVCLLFVFSA LLEYAAVNFV SRQHKELLGS SGE EMRKLF IQRAKKIDKI SRIGFPMAFL IFNMFYWIIY KIVRREDVHN Q

UniProtKB: Glycine receptor subunit alpha-1

+
Macromolecule #2: Glycine receptor subunit beta,Green fluorescent protein,Glycine r...

MacromoleculeName: Glycine receptor subunit beta,Green fluorescent protein,Glycine receptor beta
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 76.584531 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: KSSKKGKGKK KQYLCPSQQS AEDLARVPAN STSNILNRLL VSYDPRIRPN FKGIPVDVVV NIFINSFGSI QETTMDYRVN IFLRQKWND PRLKLPSDFR GSDALTVDPT MYKCLWKPDL FFANEKSANF HDVTQENILL FIFRDGDVLV SMRLSITLSC P LDLTLFPM ...String:
KSSKKGKGKK KQYLCPSQQS AEDLARVPAN STSNILNRLL VSYDPRIRPN FKGIPVDVVV NIFINSFGSI QETTMDYRVN IFLRQKWND PRLKLPSDFR GSDALTVDPT MYKCLWKPDL FFANEKSANF HDVTQENILL FIFRDGDVLV SMRLSITLSC P LDLTLFPM DTQRCKMQLE SFGYTTDDLR FIWQSGDPVQ LEKIALPQFD IKKEDIEYGN CTKYYKGTGY YTCVEVIFTL RR QVGFYMM GVYAPTLLIV VLSWLSFWIN PDASAARVPL GIFSVLSLAS ECTTLAAELP KVSYVKALDV WLIACLLFGF ASL VEYAVV QVMLNGGSSA AAVSKGEELF TGVVPILVEL DGDVNGHKFS VSGEGEGDAT YGKLTLKFIC TTGKLPVPWP TLVT TFSYG VQCFSRYPDH MKQHDFFKSA MPEGYVQERT IFFKDDGNYK TRAEVKFEGD TLVNRIELKG IDFKEDGNIL GHKLE YNYN SHNVYIMADK QKNGIKVNFK IRHNIEDGSV QLADHYQQNT PIGDGPVLLP DNHYLSTQSA LSKDPNEKRD HMVLLE FVT AAGITHGMDE LYKSGSGSGV GETRCKKVCT SKSDLRSNDF SIVGSLPRDF ELSNYDCYGK PIEVNNGLGK SQAKNNK KP PPAKPVIPTA AKRIDLYARA LFPFCFLFFN VIYWSIYL

UniProtKB: Glycine receptor subunit beta, Green fluorescent protein, Glycine receptor beta

+
Macromolecule #3: GLYCINE

MacromoleculeName: GLYCINE / type: ligand / ID: 3 / Number of copies: 5 / Formula: GLY
Molecular weightTheoretical: 75.067 Da
Chemical component information

ChemComp-GLY:
GLYCINE

+
Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 5 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

+
Macromolecule #5: nonane

MacromoleculeName: nonane / type: ligand / ID: 5 / Number of copies: 4 / Formula: DD9
Molecular weightTheoretical: 128.255 Da
Chemical component information

ChemComp-DD9:
nonane

+
Macromolecule #6: HEPTANE

MacromoleculeName: HEPTANE / type: ligand / ID: 6 / Number of copies: 6 / Formula: HP6
Molecular weightTheoretical: 100.202 Da
Chemical component information

ChemComp-HP6:
HEPTANE

+
Macromolecule #7: HEXANE

MacromoleculeName: HEXANE / type: ligand / ID: 7 / Number of copies: 13 / Formula: HEX
Molecular weightTheoretical: 86.175 Da
Chemical component information

ChemComp-HEX:
HEXANE

+
Macromolecule #8: UNDECANE

MacromoleculeName: UNDECANE / type: ligand / ID: 8 / Number of copies: 6 / Formula: UND
Molecular weightTheoretical: 156.308 Da
Chemical component information

ChemComp-UND:
UNDECANE

+
Macromolecule #9: N-BUTANE

MacromoleculeName: N-BUTANE / type: ligand / ID: 9 / Number of copies: 8 / Formula: NBU
Molecular weightTheoretical: 58.122 Da
Chemical component information

ChemComp-NBU:
N-BUTANE

+
Macromolecule #10: DECANE

MacromoleculeName: DECANE / type: ligand / ID: 10 / Number of copies: 3 / Formula: D10
Molecular weightTheoretical: 142.282 Da
Chemical component information

ChemComp-D10:
DECANE

+
Macromolecule #11: N-OCTANE

MacromoleculeName: N-OCTANE / type: ligand / ID: 11 / Number of copies: 2 / Formula: OCT
Molecular weightTheoretical: 114.229 Da
Chemical component information

ChemComp-OCT:
N-OCTANE

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration6 mg/mL
BufferpH: 8
Component:
ConcentrationFormulaName
200.0 mMNaClsodium chloride
20.0 mMTris-HClTris-HCl
0.06 % w/vdigitonindigitonin
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 70 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 %

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 69.6 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: GATAN LIQUID NITROGEN / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7mly

Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.63 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 21676
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

-
Atomic model buiding 1

Initial modelPDB ID:

7mly


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL
Output model

PDB-8dn5:
Cryo-EM structure of human Glycine Receptor alpha1-beta heteromer, glycine-bound state1(open state)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more