[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleStructural bases for stoichiometry-selective calcium potentiation of a neuronal nicotinic receptor.
Journal, issue, pagesBr J Pharmacol, Vol. 181, Issue 13, Page 1973-1992, Year 2024
Publish dateMar 7, 2024
AuthorsSimone Mazzaferro / Guipeun Kang / Kathiresan Natarajan / Ryan E Hibbs / Steven M Sine /
PubMed AbstractBACKGROUND AND PURPOSE: α4β2 nicotinic acetylcholine (nACh) receptors assemble in two stoichiometric forms, one of which is potentiated by calcium. The sites of calcium binding that underpin ...BACKGROUND AND PURPOSE: α4β2 nicotinic acetylcholine (nACh) receptors assemble in two stoichiometric forms, one of which is potentiated by calcium. The sites of calcium binding that underpin potentiation are not known.
EXPERIMENTAL APPROACH: To identify calcium binding sites, we applied cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) simulations to each stoichiometric form of the α4β2 nACh receptor in the presence of calcium ions. To test whether the identified calcium sites are linked to potentiation, we generated mutants of anionic residues at the sites, expressed wild type and mutant receptors in clonal mammalian fibroblasts, and recorded ACh-elicited single-channel currents with or without calcium.
KEY RESULTS: Both cryo-EM and MD simulations show calcium bound to a site between the extracellular and transmembrane domains of each α4 subunit (ECD-TMD site). Substituting alanine for anionic residues at the ECD-TMD site abolishes stoichiometry-selective calcium potentiation, as monitored by single-channel patch clamp electrophysiology. Additionally, MD simulation reveals calcium association at subunit interfaces within the extracellular domain. Substituting alanine for anionic residues at the ECD sites reduces or abolishes stoichiometry-selective calcium potentiation.
CONCLUSIONS AND IMPLICATIONS: Stoichiometry-selective calcium potentiation of the α4β2 nACh receptor is achieved by calcium association with topographically distinct sites framed by anionic residues within the α4 subunit and between the α4 and β2 subunits. Stoichiometry-selective calcium potentiation could result from the greater number of calcium sites in the stoichiometric form with three rather than two α4 subunits. The results are relevant to modulation of signalling via α4β2 nACh receptors in physiological and pathophysiological conditions.
External linksBr J Pharmacol / PubMed:38454578
MethodsEM (single particle)
Resolution2.35 - 3.41 Å
Structure data

EMDB-40752, PDB-8ssz:
The 2alpha3beta stoichiometry of full-length human alpha4beta2 nicotinic acetylcholine receptor in complex with acetylcholine and calcium
Method: EM (single particle) / Resolution: 2.64 Å

EMDB-40753, PDB-8st0:
The 2alpha3beta stoichiometry of full-length human alpha4beta2 nicotinic acetylcholine receptor in complex with acetylcholine
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-40754, PDB-8st1:
The 3alpha2beta stoichiometry of human alpha4beta2 nicotinic acetylcholine receptor in complex with acetylcholine and calcium
Method: EM (single particle) / Resolution: 3.41 Å

EMDB-40755, PDB-8st2:
The 3alpha2beta stoichiometry of human alpha4beta2 nicotinic acetylcholine receptor in complex with acetylcholine
Method: EM (single particle) / Resolution: 2.94 Å

EMDB-40756, PDB-8st3:
The 2alpha3beta stoichiometry of human alpha4beta2 nicotinic acetylcholine receptor in complex with acetylcholine and calcium
Method: EM (single particle) / Resolution: 2.93 Å

EMDB-40757, PDB-8st4:
The 2alpha3beta stoichiometry of human alpha4beta2 nicotinic acetylcholine receptor in complex with acetylcholine
Method: EM (single particle) / Resolution: 2.35 Å

Chemicals

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

ChemComp-ACH:
ACETYLCHOLINE / neurotransmitter*YM

ChemComp-CA:
Unknown entry

ChemComp-NA:
Unknown entry

ChemComp-OCT:
N-OCTANE

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsTRANSPORT PROTEIN / cys-loop ligand-gated pentameric ion channels / cation-selective channel / acetylcholine / calcium

+
About Yorodumi Papers

-
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 Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more