Conformational plasticity of human acid-sensing ion channel 1a.
Overview
- Vollum Institute, Oregon Health and Science University, Portland, OR USA
- Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
- Department of Biomedical and Clinical Sciences, Linköping University, Linkoping, Sweden
- Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR USA
Abstract
Acid-sensing ion channels (ASICs) are typically activated by acidic environments and contribute to nociception and synaptic plasticity. ASIC1a is the most abundant subunit in the central nervous system and forms homomeric channels permeable to Na+ and Ca2+, making it a compelling therapeutic target for acidotic pathologies including stroke and traumatic brain injury. However, a complete conformational library of human ASIC1a has yet to be described. Here we show that human ASIC1a adopts six major conformations, resolved by cryo-electron microscopy across a pH range between 8.5 and 5.7 and in the presence of a toxin agonist and a gating-modifying amino acid substitution. These major conformations establish linear transmembrane helices to be associated with an open state, delineate mechanistic differences between proton and toxin activation and demonstrate that desensitization involves unexpected conformational diversity in the transmembrane domain. Together, they provide a three-dimensional framework to integrate previous structure–function studies on ASIC.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
The paper's code and data availability statement is in the Data section.
Tracing map
A tracing map links a paper to the code its authors published: this paper has none, so it has no map.
Data
Datasets cited
- ebi.ac.uk/
pdbe/ , at EMBL-EBI; found in “Data availability”entry - figshare:32680923, at figshare; found in “Data availability”
Data availability
Cryo-EM maps and atomic models were deposited to the Protein Data Bank and EM Data Bank and are publicly available as of the date of publication through accession codes PDB 9E4A (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 2, 28 September 2026
- Publisher: n/a → Nature Portfolio
- Funding: added Howard Hughes Medical Institute; Lundbeckfonden: R313-2019-571; H. Lundbeck A/S; National Institutes of Health: 1r24gm154185-01
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 3 keywords, 7 MeSH terms, 64 references, 1 RRID.
Cite
This paper
Cahill, J., Hartfield, K. A., Heusser, S. A., Ritter, N., Poulsen, M. H., Yoshioka, C., Pless, S. A., & Baconguis, I. (2026). Conformational plasticity of human acid-sensing ion channel 1a. Nature structural & molecular biology, 33(8), 1171-1182. https://
BibTeX
@article{cahill2026confo
author = {Cahill, James and Hartfield, Kimberly A and Heusser, Stephanie Andrea and Ritter, Nadine and Poulsen, Mette Homann and Yoshioka, Craig and Pless, Stephan Alexander and Baconguis, Isabelle},
title = {{Conformational plasticity of human acid-sensing ion channel 1a}},
journal = {Nature structural \& molecular biology},
year = {2026},
month = jul,
volume = {33},
number = {8},
pages = {1171--1182},
publisher = {Nature Portfolio},
issn = {1545-9993},
doi = {10.1038/
url = {https://
pmid = {42463865},
pmcid = {PMC13468109}
}
RIS
TY - JOUR
AU - Cahill, James
AU - Hartfield, Kimberly A
AU - Heusser, Stephanie Andrea
AU - Ritter, Nadine
AU - Poulsen, Mette Homann
AU - Yoshioka, Craig
AU - Pless, Stephan Alexander
AU - Baconguis, Isabelle
TI - Conformational plasticity of human acid-sensing ion channel 1a
T2 - Nature structural & molecular biology
J2 - Nat Struct Mol Biol
PY - 2026
DA - 2026/
VL - 33
IS - 8
SP - 1171
EP - 1182
SN - 1545-9993
PB - Nature Portfolio
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1038/
"type": "article-journal",
"title": "Conformational plasticity of human acid-sensing ion channel 1a",
"container-title": "Nature structural & molecular biology",
"author": [
{
"family": "Cahill",
"given": "James"
},
{
"family": "Hartfield",
"given": "Kimberly A"
},
{
"family": "Heusser",
"given": "Stephanie Andrea"
},
{
"family": "Ritter",
"given": "Nadine"
},
{
"family": "Poulsen",
"given": "Mette Homann"
},
{
"family": "Yoshioka",
"given": "Craig"
},
{
"family": "Pless",
"given": "Stephan Alexander"
},
{
"family": "Baconguis",
"given": "Isabelle"
}
],
"container-title-short":
"volume": "33",
"issue": "8",
"page": "1171-1182",
"DOI": "10.1038/
"PMID": "42463865",
"PMCID": "PMC13468109",
"ISSN": "1545-9993",
"publisher": "Nature Portfolio",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
7,
16
]
]
}
}
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.1038/s41594-026-01866-9 [code]
- Structural and mechanistic insights into gating and allosteric modulation of GluN1-GluN3A NMDA receptors.Journal: Nature structural & molecular biologyIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 6 references
- [2] doi:10.1038/s41467-026-76831-7
- Structural origins of species-specific differences in TRPV2 activation.Journal: Nature communicationsIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 5 references
- [3] doi:10.1038/s41467-026-70575-0
- Structure of a pH-sensitive pentameric ligand-gated ion channel from the Sarcoptes scabies mite.Journal: Nature communicationsIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 5 references
- [4] doi:10.1038/s41467-026-74814-2
- Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload.Journal: Nature communicationsIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 5 references
- [5] doi:10.1038/s41594-026-01789-5 [code]
- Calcium dependent activation of the TMEM16F scramblase and ion channel.Journal: Nature structural & molecular biologyIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 4 references
- [6] doi:10.1038/s41467-026-72780-3
- Structural basis for the transport mechanism and cholesterol modulation of the human proline transporter.Journal: Nature communicationsIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 4 references
- [7] doi:10.1038/s41467-026-75564-x
- Cooperative mechanism of neurotransmitter recognition and transport by the human vesicular polyamine transporter.Journal: Nature communicationsIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 4 references
- [8] doi:10.1038/s41467-026-75806-y [code]
- Cryo-EM insights into isoform-specific properties of the IP&
lt;sub& gt;3& lt;/ sub& gt;R2 channel. Journal: Nature communicationsIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 4 references - [9] doi:10.1038/s41467-026-74087-9 [code]
- Cryo-EM structures of heteromeric Kir4.1/
5.1 channel suggest mechanisms of inward rectification and channel blockage. Journal: Nature communicationsIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 4 references - [10] doi:10.1038/s41467-026-75877-x
- Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.Journal: Nature communicationsIn common: ebi.ac.uk/pdbe/entry, histology / microscopy, cellular / molecular, 4 references
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.
Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.