[English] 日本語
Yorodumi
- PDB-7kox: Alpha-7 nicotinic acetylcholine receptor bound to epibatidine and... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7kox
TitleAlpha-7 nicotinic acetylcholine receptor bound to epibatidine and PNU-120596 in the activated state
ComponentsNeuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562 fusion
KeywordsMEMBRANE PROTEIN / Cys-loop receptor
Function / homology
Function and homology information


sensory processing / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine-gated channel complex / regulation of amyloid fibril formation / short-term memory / positive regulation of CoA-transferase activity / acetylcholine receptor activity / dendritic spine organization ...sensory processing / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine-gated channel complex / regulation of amyloid fibril formation / short-term memory / positive regulation of CoA-transferase activity / acetylcholine receptor activity / dendritic spine organization / acetylcholine binding / chloride channel regulator activity / regulation of amyloid precursor protein catabolic process / acetylcholine receptor signaling pathway / acetylcholine-gated monoatomic cation-selective channel activity / positive regulation of amyloid-beta formation / negative regulation of amyloid-beta formation / plasma membrane raft / modulation of excitatory postsynaptic potential / positive regulation of excitatory postsynaptic potential / response to amyloid-beta / negative regulation of tumor necrosis factor production / toxic substance binding / monoatomic ion transport / monoatomic ion transmembrane transport / positive regulation of protein metabolic process / positive regulation of long-term synaptic potentiation / electron transport chain / synapse organization / response to nicotine / calcium channel activity / memory / cognition / intracellular calcium ion homeostasis / positive regulation of angiogenesis / calcium ion transport / monoatomic ion channel activity / amyloid-beta binding / postsynapse / postsynaptic membrane / positive regulation of MAPK cascade / periplasmic space / electron transfer activity / learning or memory / positive regulation of ERK1 and ERK2 cascade / response to hypoxia / neuron projection / iron ion binding / positive regulation of protein phosphorylation / synapse / heme binding / positive regulation of cell population proliferation / 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 / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / Neurotransmitter-gated ion-channel transmembrane domain superfamily / Neuronal acetylcholine receptor ...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 / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / 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
EPIBATIDINE / Soluble cytochrome b562 / Neuronal acetylcholine receptor subunit alpha-7
Similarity search - Component
Biological speciesHomo sapiens (human)
Escherichia coli (E. coli)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å
AuthorsNoviello, C.M. / Hibbs, R.E. / Gharpure, A. / Mukhtasimova, N. / Baxter, L. / Cabuco, R. / Borek, D. / Sine, S.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)NS095899 United States
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)NS077983 United States
CitationJournal: Cell / Year: 2021
Title: Structure and gating mechanism of the α7 nicotinic acetylcholine receptor.
Authors: Colleen M Noviello / Anant Gharpure / Nuriya Mukhtasimova / Rico Cabuco / Leah Baxter / Dominika Borek / Steven M Sine / Ryan E Hibbs /
Abstract: The α7 nicotinic acetylcholine receptor plays critical roles in the central nervous system and in the cholinergic inflammatory pathway. This ligand-gated ion channel assembles as a homopentamer, is ...The α7 nicotinic acetylcholine receptor plays critical roles in the central nervous system and in the cholinergic inflammatory pathway. This ligand-gated ion channel assembles as a homopentamer, is exceptionally permeable to Ca, and desensitizes faster than any other Cys-loop receptor. The α7 receptor has served as a prototype for the Cys-loop superfamily yet has proven refractory to structural analysis. We present cryo-EM structures of the human α7 nicotinic receptor in a lipidic environment in resting, activated, and desensitized states, illuminating the principal steps in the gating cycle. The structures also reveal elements that contribute to its function, including a C-terminal latch that is permissive for channel opening, and an anionic ring in the extracellular vestibule that contributes to its high conductance and calcium permeability. Comparisons among the α7 structures provide a foundation for mapping the gating cycle and reveal divergence in gating mechanisms in the Cys-loop receptor superfamily.
History
DepositionNov 10, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 17, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 31, 2021Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_PubMed / _citation.title
Revision 2.0May 5, 2021Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations / Polymer sequence / Refinement description / Structure summary
Category: atom_site / em_software ...atom_site / em_software / entity / entity_poly / entity_poly_seq / pdbx_branch_scheme / pdbx_nonpoly_scheme / pdbx_poly_seq_scheme / pdbx_struct_assembly_prop / pdbx_struct_conn_angle / pdbx_validate_close_contact / pdbx_validate_rmsd_angle / pdbx_validate_torsion / refine_ls_restr / software / struct / struct_conn / struct_mon_prot_cis / struct_ref_seq_dif / struct_sheet_range
Item: _em_software.category / _entity.formula_weight ..._em_software.category / _entity.formula_weight / _entity_poly.pdbx_seq_one_letter_code / _entity_poly.pdbx_seq_one_letter_code_can / _entity_poly_seq.mon_id / _pdbx_branch_scheme.auth_asym_id / _pdbx_branch_scheme.auth_seq_num / _pdbx_nonpoly_scheme.auth_seq_num / _pdbx_poly_seq_scheme.auth_mon_id / _pdbx_poly_seq_scheme.mon_id / _pdbx_poly_seq_scheme.pdb_mon_id / _pdbx_struct_assembly_prop.value / _pdbx_struct_conn_angle.value / _pdbx_validate_close_contact.auth_asym_id_1 / _pdbx_validate_close_contact.auth_asym_id_2 / _pdbx_validate_rmsd_angle.angle_deviation / _pdbx_validate_rmsd_angle.angle_value / _pdbx_validate_torsion.phi / _pdbx_validate_torsion.psi / _refine_ls_restr.dev_ideal / _refine_ls_restr.number / _software.version / _struct.pdbx_descriptor / _struct_conn.pdbx_dist_value / _struct_mon_prot_cis.pdbx_omega_angle / _struct_sheet_range.beg_auth_comp_id / _struct_sheet_range.beg_auth_seq_id / _struct_sheet_range.beg_label_comp_id / _struct_sheet_range.beg_label_seq_id / _struct_sheet_range.end_auth_comp_id / _struct_sheet_range.end_auth_seq_id / _struct_sheet_range.end_label_comp_id / _struct_sheet_range.end_label_seq_id
Description: Sequence discrepancy
Details: The sequence used for the original model was taken from the literature reference; it was created during quarantine and I did not have access to the lab-confirmed sequence. There are two ...Details: The sequence used for the original model was taken from the literature reference; it was created during quarantine and I did not have access to the lab-confirmed sequence. There are two amino acids different between these two reference sequences. The correct sequence corresponds to UniProt code P36544, while the literature cites U40583.1. The amino acids have been changed accordingly.
Provider: author / Type: Coordinate replacement
Revision 2.1May 12, 2021Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.page_first

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-22983
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Neuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562 fusion
B: Neuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562 fusion
C: Neuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562 fusion
D: Neuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562 fusion
E: Neuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562 fusion
hetero molecules


Theoretical massNumber of molelcules
Total (without water)324,73930
Polymers319,1615
Non-polymers5,57825
Water905
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area34330 Å2
ΔGint-169 kcal/mol
Surface area85690 Å2

-
Components

-
Protein , 1 types, 5 molecules ABCDE

#1: Protein
Neuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562 fusion / Cytochrome b-562


Mass: 63832.293 Da / Num. of mol.: 5
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Escherichia coli (E. coli)
Gene: CHRNA7, NACHRA7, cybC / Production host: Homo sapiens (human) / References: UniProt: P36544, UniProt: P0ABE7

-
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: obtained synthetically
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
#3: 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: isolated from a natural source / 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

#4: Chemical
ChemComp-EPJ / EPIBATIDINE / (2R)-2-(6-CHLOROPYRIDIN-3-YL)-7-AZABICYCLO[2.2.1]HEPTANE


Mass: 208.687 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C11H13ClN2 / Comment: alkaloid*YM
#5: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: Ca
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 5 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: alpha-7 nicotinic receptor in complex with epibatidine and PNU-120596
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
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
Image recordingElectron dose: 45 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.19_4080: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 2004527 / Symmetry type: POINT
RefinementHighest resolution: 2.7 Å
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.01416375
ELECTRON MICROSCOPYf_angle_d1.18122325
ELECTRON MICROSCOPYf_dihedral_angle_d13.4095850
ELECTRON MICROSCOPYf_chiral_restr0.2292570
ELECTRON MICROSCOPYf_plane_restr0.0052745

+
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://pdbjlvh1.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