ArticleCell reports2023
Structural insights into anion selectivity and activation mechanism of LRRC8 volume-regulated anion channels.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- State-dependent inhibition of LRRC8 volume-regulated anion channels by DCPIB.The Journal of general physiology · 2026Article
- The intracellular subdomain of the volume-regulated anion channel subunit LRRC8A is a hotspot of channel activation.Nature communications · 2026Article
- Structures of the volume-regulated anion channel LRRC8A/D in activating and inhibiting conditions.Nature communications · 2026Article
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels and regulates cGAMP transport.Molecular cell · 2025Article
- Assembly and lipid-gating of LRRC8A:D volume-regulated anion channels.Nature communications · 2025Article
- Structural basis of PANX1 permeation and positive modulation by mefloquine.Nature communications · 2025Article
- A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs.Communications biology · 2025Article
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels.bioRxiv : the preprint server for biology · 2025Article
- Recent advances in the structure, function and regulation of the volume-regulated anion channels and their role in immunity.The Journal of physiology · 2025Review
- Recent advances in structural characterization of volume-regulated anion channels (VRACs).The Journal of physiology · 2025Review
- A mechanism of CALHM1 ion channel gating.American journal of physiology. Cell physiology · 2025Article
- Recent insights on the impact of SWELL1 on metabolic syndromes.Frontiers in pharmacology · 2025Review
- Activation of osmo-sensitive LRRC8 anion channels in macrophages is important for micro-crystallin joint inflammation.Nature communications · 2024Article
- Interactomic exploration of LRRC8A in volume-regulated anion channels.Cell death discovery · 2024Article
- Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC: part 2: its activation mechanisms and essential roles in organic signal release.The journal of physiological sciences : JPS · 2024Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Volume-regulated anion channels (VRACs) are hexamers of LRRC8 proteins that are crucial for cell volume regulation. N termini (NTs) of the obligatory LRRC8A subunit modulate VRACs activation and ion selectivity, but the underlying mechanisms remain poorly understood. Here, we report a 2.8-Å cryo-electron microscopy structure of human LRRC8A that displays well-resolved NTs. Amino-terminal halves of NTs fold back into the pore and constrict the permeation path, thereby determining ion selectivity together with an extracellular selectivity filter with which it works in series. They also interact with pore-surrounding helices and support their compact arrangement. The C-terminal halves of NTs interact with intracellular loops that are crucial for channel activation. Molecular dynamics simulations indicate that low ionic strength increases NT mobility and expands the radial distance between pore-surrounding helices. Our work suggests an unusual pore architecture with two selectivity filters in series and a mechanism for VRAC activation by cell swelling.
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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 OpenQuestion graph.