22QT

Cryo-EM structure of the Deg-3/Des-2 betaine-bound intermediate state

Summary for 22QT

• Entry DOI: 10.2210/pdb22qt/pdb
• EMDB information: 68608
• Descriptor: Acetylcholine receptor subunit alpha-type des-2, Acetylcholine receptor subunit alpha-type deg-3, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: nachr, betaine, membrane protein
• Biological source: Caenorhabditis elegans; More
• Total number of polymer chains: 5
• Total formula weight: 321871.84

Authors

Ning, Y.,Ge, J.,Yu, J. (deposition date: 2026-01-21, release date: 2026-08-12, Last modification date: 2026-10-07)

Primary citation

Ning, Y.,Jiang, Q.,Lu, Z.,Yu, J.,Ge, J.
Structural basis of ligand recognition and gating in a heteromeric Deg-3/Des-2 nicotinic acetylcholine receptor.
Proc.Natl.Acad.Sci.USA, 123:e2608998123-e2608998123, 2026

PubMed Abstract: During evolution, nicotinic acetylcholine receptors (nAChRs) have diversified in subunit composition and ligand selectivity, enabling a conserved ion channel scaffold to support a broad range of signaling functions beyond classical synaptic transmission. Deg-3/Des-2 is a nematode-specific, calcium-permeable heteromeric α-type nicotinic receptor in sensory neurons to mediate chemosensation, nociception, and mechanotransduction, and represents a promising anthelmintic target. Here, we report cryo-electron microscopy structures of Deg-3/Des-2 in its apo, agonist-bound intermediate and agonist-bound open states. Deg-3/Des-2 adopts a 2Deg-3:3Des-2 stoichiometry. Five agonist molecules occupy intersubunit orthosteric sites, driving channel opening primarily through rotational rearrangements of the upper M2 helices that relieve a conserved hydrophobic gate and enable calcium permeation. We further identify a Deg-3-specific N-terminal helix that regulates desensitization and a negatively charged extracellular vestibular helix that governs calcium permeability. Together, these structures reveal how evolutionary tuning of ligand recognition, ion selectivity, and gating within a conserved nicotinic receptor framework.

PubMed: 42623446
DOI: 10.1073/pnas.2608998123

Experimental method

ELECTRON MICROSCOPY (2.66 Å)