[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 analysis reveals TLR7 dynamics underlying antagonism.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 5204, Year 2020
Publish dateOct 15, 2020
AuthorsShingo Tojo / Zhikuan Zhang / Hiroyuki Matsui / Masahiro Tahara / Mitsunori Ikeguchi / Mami Kochi / Mami Kamada / Hideki Shigematsu / Akihisa Tsutsumi / Naruhiko Adachi / Takuma Shibata / Masaki Yamamoto / Masahide Kikkawa / Toshiya Senda / Yoshiaki Isobe / Umeharu Ohto / Toshiyuki Shimizu /
PubMed AbstractToll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs and nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus ...Toll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs and nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus erythematosus (SLE). Here, by modifying potent TLR7 agonists, we develop a series of TLR7-specific antagonists as promising therapeutic agents for SLE. These compounds protect mice against lethal autoimmunity. Combining crystallography and cryo-electron microscopy, we identify the open conformation of the receptor and reveal the structural equilibrium between open and closed conformations that underlies TLR7 antagonism, as well as the detailed mechanism by which TLR7-specific antagonists bind to their binding pocket in TLR7. Our work provides small-molecule TLR7-specific antagonists and suggests the TLR7-targeting strategy for treating autoimmune diseases.
External linksNat Commun / PubMed:33060576 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.6 - 4.4 Å
Structure data

EMDB-0999:
Cryo-EM reconstruction of TLR7/Cpd-3 (SM-394830) complex in closed form
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-1000:
Cryo-EM reconstruction of TLR7/Cpd-6 (DSR-139293) complex in closed form
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-30000:
Cryo-EM reconstruction of TLR7/Cpd-6 (DSR-139293) complex in open form
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-30001:
Cryo-EM reconstruction of TLR7/Cpd-7 (DSR-139970) complex in open form
Method: EM (single particle) / Resolution: 4.1 Å

30002

6lw1

EMDB-30002, PDB-6lw1:
Cryo-EM structure of TLR7/Cpd-7 (DSR-139970) complex in open form
Method: EM (single particle) / Resolution: 2.8 Å

PDB-6lvx:
Crystal structure of TLR7/Cpd-1 (SM-374527) complex
Method: X-RAY DIFFRACTION / Resolution: 2.77 Å

PDB-6lvy:
Crystal structure of TLR7/Cpd-2 (SM-360320) complex
Method: X-RAY DIFFRACTION / Resolution: 2.6 Å

PDB-6lvz:
Crystal structure of TLR7/Cpd-3 (SM-394830) complex
Method: X-RAY DIFFRACTION / Resolution: 2.83 Å

PDB-6lw0:
Crystal structure of TLR7/Cpd-6 (DSR-139293) complex
Method: X-RAY DIFFRACTION / Resolution: 2.6 Å

Chemicals

ChemComp-EWL:
6-azanyl-2-butoxy-9-(phenylmethyl)-7H-purin-8-one

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-SO4:
SULFATE ION / Sulfate

ChemComp-HOH:
WATER / Water

ChemComp-EWU:
6-azanyl-2-(2-methoxyethoxy)-9-(phenylmethyl)-7H-purin-8-one

ChemComp-EWX:
6-azanyl-2-(2-methoxyethoxy)-9-(pyridin-3-ylmethyl)-7H-purin-8-one

ChemComp-EX0:
2-ethoxy-8-(5-fluoranylpyridin-3-yl)-9-[[4-[[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]phenyl]methyl]purin-6-amine

ChemComp-EX3:
2-ethoxy-8-(5-fluoranylpyridin-3-yl)-6-methyl-9-[[4-[[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]phenyl]methyl]purine

Source
  • macaca mulatta (Rhesus monkey)
KeywordsIMMUNE SYSTEM / TLR7 / agonist / antagonist

+
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