Evidence map›Paper›PMID 37645939›Full record

ArticlebioRxiv : the preprint server for biology2023

CryoEM structures of the human CLC-2 voltage gated chloride channel reveal a ball and chain gating mechanism.

Mengyuan Xu, Torben Neelands, Alexander S Powers, Yan Liu, Steven D Miller, Grigore Pintilie, J Du Bois, Ron O Dror, Wah Chiu, Merritt Maduke

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Mengyuan XuDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.
Torben NeelandsDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.
Alexander S PowersDepartment of Chemistry, Stanford University, Stanford, CA 94305.
Yan LiuDivision of CryoEM and Bioimaging, SSRL, SLAC National Accelerator Laboratory, Stanford University, Menlo Park 94025.
Steven D MillerDepartment of Chemistry, Stanford University, Stanford, CA 94305.
Grigore PintilieDepartment of Bioengineering and Department of Microbiology and Immunology, Stanford University, Stanford, 94305.
J Du BoisDepartment of Chemistry, Stanford University, Stanford, CA 94305.
Ron O DrorDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.
Wah ChiuDivision of CryoEM and Bioimaging, SSRL, SLAC National Accelerator Laboratory, Stanford University, Menlo Park 94025.ORCID 0000-0002-8910-3078
Merritt MadukeDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.ORCID 0000-0001-7787-306X
Stanford University · USSLAC National Accelerator Laboratory · US

Funding

The Stanford-SLAC CryoEM Center supplementU24GM129541 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH, HEDMAN, BRITT · 2018 to 2023
$54.8M
Small-molecule probes for study of CLC-2 chloride-channel function in the central nervous systemR01NS113611 · NINDS · STANFORD UNIVERSITY · PI DU BOIS, JUSTIN, HUGUENARD, JOHN R · 2020 to 2024
$2.8M
CLC-2 voltage-gated chloride channel structure and ligand recognitionR21NS125767 · NINDS · STANFORD UNIVERSITY · PI MADUKE, MERRITT C · 2021 to 2021
$433k
NIGMS NIH HHS U24 GM129541NINDS NIH HHS R01 NS113611NINDS NIH HHS R21 NS125767
6 · The paper itself

Abstract

CLC-2 is a voltage-gated chloride channel that contributes to electrical excitability and ion homeostasis in many different mammalian tissues and cell types. Among the nine mammalian CLC homologs, CLC-2 is uniquely activated by hyperpolarization, rather than depolarization, of the plasma membrane. The molecular basis for the divergence in polarity of voltage gating mechanisms among closely related CLC homologs has been a long-standing mystery, in part because few CLC channel structures are available, and those that exist exhibit high conformational similarity. Here, we report cryoEM structures of human CLC-2 at 2.46 - 2.76 Å, in the presence and absence of the potent and selective inhibitor AK-42. AK-42 binds within the extracellular entryway of the Cl

Indexed as

chloride channelcryo-electron microscopyelectrophysiology

Identifiers

PMID37645939
PMCPMC10462068
OpenAlexW4385829359

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.