[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

TitleDe novo variants in LRRC8C resulting in constitutive channel activation cause a human multisystem disorder.
Journal, issue, pagesEMBO J, Vol. 44, Issue 2, Page 413-436, Year 2025
Publish dateDec 2, 2024
AuthorsMathieu Quinodoz / Sonja Rutz / Virginie Peter / Livia Garavelli / A Micheil Innes / Elena F Lehmann / Stephan Kellenberger / Zhong Peng / Angelica Barone / Belinda Campos-Xavier / Sheila Unger / Carlo Rivolta / Raimund Dutzler / Andrea Superti-Furga /
PubMed AbstractVolume-regulated anion channels (VRACs) are multimeric proteins composed of different paralogs of the LRRC8 family. They are activated in response to hypotonic swelling, but little is known about ...Volume-regulated anion channels (VRACs) are multimeric proteins composed of different paralogs of the LRRC8 family. They are activated in response to hypotonic swelling, but little is known about their specific functions. We studied two human individuals with the same congenital syndrome affecting blood vessels, brain, eyes, and bones. The LRRC8C gene harbored de novo variants in both patients, located in a region of the gene encoding the boundary between the pore and a cytoplasmic domain, which is depleted of sequence variations in control subjects. When studied by cryo-EM, both LRRC8C mutant proteins assembled as their wild-type counterparts, but showed increased flexibility, suggesting a destabilization of subunit interactions. When co-expressed with the obligatory LRRC8A subunit, the mutants exhibited enhanced activation, resulting in channel activity even at isotonic conditions in which wild-type channels are closed. We conclude that structural perturbations of LRRC8C impair channel gating and constitute the mechanistic basis of the dominant gain-of-function effect of these pathogenic variants. The pleiotropic phenotype of this novel clinical entity associated with monoallelic LRRC8C variants indicates the fundamental roles of VRACs in different tissues and organs.
External linksEMBO J / PubMed:39623139 / PubMed Central
MethodsEM (single particle)
Resolution3.41 - 7.32 Å
Structure data

19495

8rts

EMDB-19495, PDB-8rts:
Structure of a homomeric human LRRC8C Volume-Regulated Anion Channel
Method: EM (single particle) / Resolution: 3.73 Å

50072

9ezc

EMDB-50072, PDB-9ezc:
Structure of the extracellular subdomain of a homomeric LRRC8C truncation disease mutant
Method: EM (single particle) / Resolution: 3.41 Å

EMDB-50073: Cryo-EM structure of a homomeric LRRC8C truncation disease mutant, with C1 symmetry
Method: EM (single particle) / Resolution: 7.32 Å

EMDB-50074: Cryo-EM structure of a homomeric LRRC8C truncation disease mutant, with C7 symmetry
Method: EM (single particle) / Resolution: 4.95 Å

50123

9f16

EMDB-50123, PDB-9f16:
Structure of a homomeric LRRC8C point mutation disease mutant
Method: EM (single particle) / Resolution: 4.4 Å

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Anion channel / Volume regulation / disease mutation / disease mutant

+
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