[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 mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites.
Journal, issue, pagesNeuron, Vol. 110, Issue 6, Page 1023-11035.e5, Year 2022
Publish dateMar 16, 2022
AuthorsWenjun Guo / Qinglin Tang / Miao Wei / Yunlu Kang / Jing-Xiang Wu / Lei Chen /
PubMed AbstractTRPC3 and TRPC6 channels are calcium-permeable non-selective cation channels that are involved in many physiological processes. The gain-of-function (GOF) mutations of TRPC6 lead to familial focal ...TRPC3 and TRPC6 channels are calcium-permeable non-selective cation channels that are involved in many physiological processes. The gain-of-function (GOF) mutations of TRPC6 lead to familial focal segmental glomerulosclerosis (FSGS) in humans, but their pathogenic mechanism remains elusive. Here, we report the cryo-EM structures of human TRPC3 in both high-calcium and low-calcium conditions. Based on these structures and accompanying electrophysiological studies, we identified both inhibitory and activating calcium-binding sites in TRPC3 that couple intracellular calcium concentrations to the basal channel activity. These calcium sensors are also structurally and functionally conserved in TRPC6. We uncovered that the GOF mutations of TRPC6 activate the channel by allosterically abolishing the inhibitory effects of intracellular calcium. Furthermore, structures of human TRPC6 in complex with two chemically distinct inhibitors bound at different ligand-binding pockets reveal different conformations of the transmembrane domain, providing templates for further structure-based drug design targeting TRPC6-related diseases such as FSGS.
External linksNeuron / PubMed:35051376
MethodsEM (single particle)
Resolution2.7 - 3.9 Å
Structure data

30903

7dxb

EMDB-30903, PDB-7dxb:
Structure of TRPC3 at 2.7 angstrom in high calcium state
Method: EM (single particle) / Resolution: 2.7 Å

30904

7dxc

EMDB-30904, PDB-7dxc:
Structure of TRPC3 at 3.06 angstrom in low calcium state
Method: EM (single particle) / Resolution: 3.06 Å

30905

7dxd

EMDB-30905, PDB-7dxd:
Structure of TRPC3 at 3.9 angstrom in 1340 nM free calcium state
Method: EM (single particle) / Resolution: 3.9 Å

30906

7dxe

EMDB-30906, PDB-7dxe:
Structure of TRPC3 gain of function mutation R803C at 3.2 angstrom in 1340nM free calcium state
Method: EM (single particle) / Resolution: 3.2 Å

30907

7dxf

EMDB-30907, PDB-7dxf:
Structure of BTDM-bound human TRPC6 nanodisc at 2.9 angstrom in high calcium state
Method: EM (single particle) / Resolution: 2.9 Å

30908

7dxg

EMDB-30908, PDB-7dxg:
Structure of SAR7334-bound TRPC6 at 2.9 angstrom
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM / POPC

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-98R:
[(2S)-2-[(E)-octadec-10-enoyl]oxy-3-oxidanyl-propyl] octadec-10-enoate

ChemComp-W99:
[2-(1,3-benzodioxol-5-ylamino)-1,3-thiazol-4-yl]-[(3R,5S)-3,5-dimethylpiperidin-1-yl]methanone

ChemComp-HOR:
4-[[(1R,2R)-2-[(3R)-3-azanylpiperidin-1-yl]-2,3-dihydro-1H-inden-1-yl]oxy]-3-chloranyl-benzenecarbonitrile

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / TRPC3 / TRPC / calcium / channel / gain of function / TRPC6 / BTDM / FSGS / SAR7334

+
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