[English] 日本語
Yorodumi
- PDB-9iir: human alpha 7 nicotinic acetylcholine receptor in complex with GA... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9iir
Titlehuman alpha 7 nicotinic acetylcholine receptor in complex with GAT107 and calcium (desensitized state)
ComponentsNeuronal acetylcholine receptor subunit alpha-7
KeywordsMEMBRANE PROTEIN / Ligand-gated ion channel / Positive allosteric modulator / Ago-PAM / Allosteric modulation / Calcium potentiation
Function / homology
Function and homology information


sensory processing / synaptic transmission involved in micturition / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / acetylcholine-gated channel complex / regulation of amyloid fibril formation / acetylcholine-gated monoatomic cation-selective channel activity / short-term memory ...sensory processing / synaptic transmission involved in micturition / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / acetylcholine-gated channel complex / regulation of amyloid fibril formation / acetylcholine-gated monoatomic cation-selective channel activity / short-term memory / cation channel complex / dendritic spine organization / chloride channel regulator activity / acetylcholine binding / regulation of amyloid precursor protein catabolic process / acetylcholine receptor signaling pathway / neurotransmitter receptor complex / positive regulation of amyloid-beta formation / negative regulation of amyloid-beta formation / positive regulation of protein metabolic process / response to amyloid-beta / monoatomic ion channel activity / ligand-gated ion channel signaling pathway / modulation of excitatory postsynaptic potential / plasma membrane raft / negative regulation of tumor necrosis factor production / positive regulation of excitatory postsynaptic potential / toxic substance binding / monoatomic ion transport / negative regulation of canonical NF-kappaB signal transduction / negative regulation of cytokine production involved in inflammatory response / positive regulation of long-term synaptic potentiation / excitatory postsynaptic potential / regulation of membrane potential / response to nicotine / synapse organization / calcium channel activity / cognition / memory / intracellular calcium ion homeostasis / positive regulation of angiogenesis / calcium ion transport / transmembrane signaling receptor activity / amyloid-beta binding / monoatomic ion transmembrane transport / chemical synaptic transmission / postsynaptic membrane / response to hypoxia / learning or memory / neuron projection / positive regulation of ERK1 and ERK2 cascade / postsynapse / positive regulation of MAPK cascade / positive regulation of cell population proliferation / synapse / dendrite / endoplasmic reticulum membrane / signal transduction / protein homodimerization activity / membrane / plasma membrane
Similarity search - Function
Nicotinic acetylcholine receptor / 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
Similarity search - Domain/homology
CHOLESTEROL / : / Neuronal acetylcholine receptor subunit alpha-7
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.93 Å
AuthorsLiu, S. / Zheng, Y. / Tian, C.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell Discov / Year: 2025
Title: Structural basis for allosteric agonism of human α7 nicotinic acetylcholine receptors.
Authors: Sanling Liu / Yining Zheng / Haopeng Chen / Xin Li / Qipeng Yan / Wenjun Mu / Yaning Fu / Huan Chen / Hongwei Hou / Lei Liu / Changlin Tian /
Abstract: The α7 nicotinic acetylcholine receptor (nAChR), a pentameric ligand-gated ion channel, plays important roles in cognition, neuroprotection, and anti-inflammation. As a potential drug target, α7 ...The α7 nicotinic acetylcholine receptor (nAChR), a pentameric ligand-gated ion channel, plays important roles in cognition, neuroprotection, and anti-inflammation. As a potential drug target, α7 nAChR has different binding sites for different ligands, particularly agonists and positive allosteric modulators (PAMs). Ago-PAMs can both directly activate and allosterically modulate α7 nAChR. However, the mechanism underlying α7 nAChR modulation by ago-PAM has yet to be fully elucidated. Here, we present cryo-EM structures of α7 nAChR in complex with the ago-PAM GAT107 and Ca in the open and desensitized states, respectively. Our results from both structural comparisons and functional assays suggest an allosteric mechanism underlying GAT107 modulation and calcium potentiation of α7 nAChR, involving local conformational changes in the ECD-TMD coupling region and a global structural rearrangement in the transmembrane domain. This work provides a new mechanism of α7 nAChR gating distinct from that of conventional agonist binding. These findings would aid in drug design and enrich our biophysical understanding of pentameric ligand-gated ion channels.
History
DepositionJun 21, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Apr 23, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Neuronal acetylcholine receptor subunit alpha-7
B: Neuronal acetylcholine receptor subunit alpha-7
C: Neuronal acetylcholine receptor subunit alpha-7
D: Neuronal acetylcholine receptor subunit alpha-7
E: Neuronal acetylcholine receptor subunit alpha-7
hetero molecules


Theoretical massNumber of molelcules
Total (without water)296,57635
Polymers288,0815
Non-polymers8,49430
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1(chain "A" and (resid 23 through 136 or resid 138 through 621))
d_2ens_1(chain "B" and (resid 23 through 136 or resid 138 through 621))
d_3ens_1(chain "C" and (resid 23 through 136 or resid 138 through 621))
d_4ens_1(chain "D" and (resid 23 through 136 or resid 138 through 621))
d_5ens_1(chain "E" and (resid 23 through 136 or resid 138 through 621))

NCS domain segments:

Ens-ID: ens_1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
d_11GLYGLYGLYGLYAA23 - 13623 - 136
d_12CYSCYSALAALAAA138 - 502138 - 502
d_13YLIYLIYLIYLIAK601
d_14CACACACAAL602
d_15NAGNAGNAGNAGAM603
d_16NAGNAGNAGNAGAN604
d_17NAGNAGNAGNAGFF1
d_18NAGNAGNAGNAGFF2
d_19CLRCLRCLRCLRAO605
d_21GLYGLYGLYGLYBB23 - 13623 - 136
d_22CYSCYSALAALABB138 - 502138 - 502
d_23YLIYLIYLIYLIBP601
d_24CACACACABQ602
d_25NAGNAGNAGNAGBR603
d_26NAGNAGNAGNAGBS604
d_27NAGNAGNAGNAGGG1
d_28NAGNAGNAGNAGGG2
d_29CLRCLRCLRCLRBT605
d_31GLYGLYGLYGLYCC23 - 13623 - 136
d_32CYSCYSALAALACC138 - 502138 - 502
d_33YLIYLIYLIYLICU601
d_34CACACACACV602
d_35NAGNAGNAGNAGCW603
d_36NAGNAGNAGNAGCX604
d_37NAGNAGNAGNAGHH1
d_38NAGNAGNAGNAGHH2
d_39CLRCLRCLRCLRCY605
d_41GLYGLYGLYGLYDD23 - 13623 - 136
d_42CYSCYSALAALADD138 - 502138 - 502
d_43YLIYLIYLIYLIDZ601
d_44CACACACADAA602
d_45NAGNAGNAGNAGDBA603
d_46NAGNAGNAGNAGDCA604
d_47NAGNAGNAGNAGII1
d_48NAGNAGNAGNAGII2
d_49CLRCLRCLRCLRDDA605
d_51GLYGLYGLYGLYEE23 - 13623 - 136
d_52CYSCYSALAALAEE138 - 502138 - 502
d_53YLIYLIYLIYLIEEA601
d_54CACACACAEFA602
d_55NAGNAGNAGNAGEGA - HA603 - 604
d_56NAGNAGNAGNAGEHA - GA604 - 603
d_57NAGNAGNAGNAGJJ1
d_58NAGNAGNAGNAGJJ2
d_59CLRCLRCLRCLREIA605

NCS oper:
IDCodeMatrixVector
1given(0.306704482402, 0.951804656634, 0.00050604735556), (-0.951804786089, 0.306704492302, 5.98392869079E-5), (-9.82516853393E-5, -0.000500011272528, 0.999999870168)-33.2784703941, 211.258255185, 0.0872341392494
2given(-0.809669739307, 0.58688570973, 0.000277424723568), (-0.586885767954, -0.809669563913, -0.000540967580368), (-9.28637873951E-5, -0.000600821701711, 0.999999815195)156.9807284, 307.774709101, 0.101434353171
3given(-0.808421645247, -0.588603776702, -0.00019377410886), (0.588603800448, -0.80842164503, -9.97297889264E-5), (-9.79498534367E-5, -0.000194679896947, 0.999999976253)307.816608468, 156.635993395, 0.0408606309539
4given(0.310186038832, -0.950675867582, -0.000126931889359), (0.950675870273, 0.310186048907, -6.88821703871E-5), (0.000104857118334, -9.93047968033E-5, 0.999999989572)210.654469974, -33.5127740985, 0.0072822445409

-
Components

-
Protein , 1 types, 5 molecules ABCDE

#1: Protein
Neuronal acetylcholine receptor subunit alpha-7


Mass: 57616.250 Da / Num. of mol.: 5
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CHRNA7, NACHRA7 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P36544

-
Sugars , 2 types, 15 molecules

#2: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 5
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#5: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Non-polymers , 3 types, 15 molecules

#3: Chemical
ChemComp-YLI / (3aR,4S,9bS)-4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide


Mass: 405.309 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C18H17BrN2O2S / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: Ca
#6: Chemical
ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C27H46O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: human alpha 7 nicotinic acetylcholine receptor in complex with GAT107
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1700 nm / Nominal defocus min: 1100 nm
Image recordingElectron dose: 54 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.93 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 101093 / Symmetry type: POINT
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 95.24 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.002216900
ELECTRON MICROSCOPYf_angle_d0.450423095
ELECTRON MICROSCOPYf_chiral_restr0.0372675
ELECTRON MICROSCOPYf_plane_restr0.00322815
ELECTRON MICROSCOPYf_dihedral_angle_d10.44976005
Refine LS restraints NCS
Ens-IDDom-IDAsym-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AAELECTRON MICROSCOPYNCS constraints8.07450895335E-11
ens_1d_3AAELECTRON MICROSCOPYNCS constraints1.07818242729E-11
ens_1d_4AAELECTRON MICROSCOPYNCS constraints9.30959834381E-11
ens_1d_5AAELECTRON MICROSCOPYNCS constraints1.22789385764E-12

+
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