9E4E

Human ASIC1a at pH 6.5 with linear transmembrane domain

Summary for 9E4E

• Entry DOI: 10.2210/pdb9e4e/pdb
• EMDB information: 47507
• Descriptor: Acid-sensing ion channel 1 (1 entity in total)
• Functional Keywords: ion channel, trimer, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 180757.88

Authors

Hartfield, K.A.,Cahill, J.,Baconguis, I. (deposition date: 2024-10-24, release date: 2026-01-21, Last modification date: 2026-07-29)

Primary citation

Cahill, J.,Hartfield, K.A.,Heusser, S.A.,Ritter, N.,Poulsen, M.H.,Yoshioka, C.,Pless, S.A.,Baconguis, I.
Conformational plasticity of human acid-sensing ion channel 1a.
Nat.Struct.Mol.Biol., 2026

PubMed 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 Ca, 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.

PubMed: 42463865
DOI: 10.1038/s41594-026-01845-0

Experimental method

ELECTRON MICROSCOPY (3.16 Å)