[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 basis for high-voltage activation and subtype-specific inhibition of human Na1.8.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 119, Issue 30, Page e2208211119, Year 2022
Publish dateJul 26, 2022
AuthorsXiaoshuang Huang / Xueqin Jin / Gaoxingyu Huang / Jian Huang / Tong Wu / Zhangqiang Li / Jiaofeng Chen / Fang Kong / Xiaojing Pan / Nieng Yan /
PubMed AbstractThe dorsal root ganglia-localized voltage-gated sodium (Na) channel Na1.8 represents a promising target for developing next-generation analgesics. A prominent characteristic of Na1.8 is the ...The dorsal root ganglia-localized voltage-gated sodium (Na) channel Na1.8 represents a promising target for developing next-generation analgesics. A prominent characteristic of Na1.8 is the requirement of more depolarized membrane potential for activation. Here we present the cryogenic electron microscopy structures of human Na1.8 alone and bound to a selective pore blocker, A-803467, at overall resolutions of 2.7 to 3.2 Å. The first voltage-sensing domain (VSD) displays three different conformations. Structure-guided mutagenesis identified the extracellular interface between VSD and the pore domain (PD) to be a determinant for the high-voltage dependence of activation. A-803467 was clearly resolved in the central cavity of the PD, clenching S6. Our structure-guided functional characterizations show that two nonligand binding residues, Thr397 on S6 and Gly1406 on S6, allosterically modulate the channel's sensitivity to A-803467. Comparison of available structures of human Na channels suggests the extracellular loop region to be a potential site for developing subtype-specific pore-blocking biologics.
External linksProc Natl Acad Sci U S A / PubMed:35858452 / PubMed Central
MethodsEM (single particle)
Resolution2.7 - 3.2 Å
Structure data

32439

7we4

EMDB-32439, PDB-7we4:
Human Nav1.8 with A-803467, class I
Method: EM (single particle) / Resolution: 2.7 Å

32451

7wel

EMDB-32451, PDB-7wel:
Human Nav1.8 with A-803467, class II
Method: EM (single particle) / Resolution: 3.2 Å

32475

7wfr

EMDB-32475, PDB-7wfr:
Human Nav1.8 with A-803467, class III
Method: EM (single particle) / Resolution: 3.0 Å

32476

7wfw

EMDB-32476, PDB-7wfw:
Apo human Nav1.8
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

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

ChemComp-95T:
5-(4-chlorophenyl)-~{N}-(3,5-dimethoxyphenyl)furan-2-carboxamide

ChemComp-CLR:
CHOLESTEROL

ChemComp-PCW:
1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / DOPC, phospholipid*YM

ChemComp-LPE:
1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE

ChemComp-P5S:
O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / voltage-gated sodium channel / Nav / activation / selectivity

+
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