9NX1

Alpha7-nicotinic acetylcholine receptor bound to conotoxin ImII

Summary for 9NX1

• Entry DOI: 10.2210/pdb9nx1/pdb
• EMDB information: 49898
• Descriptor: Alpha-conotoxin ImII, Neuronal acetylcholine receptor subunit alpha-7, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: ion channel, toxin, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 277312.90

Authors

Stowell, M.H.B.,Hibbs, R.E.,Noviello, C.M.,Bhattacharjee, B. (deposition date: 2025-03-25, release date: 2026-02-04)

Primary citation

Bhattacharjee, B.,Noviello, C.M.,Rahman, M.M.,Mayer, J.P.,Gajewiak, J.,McIntosh, J.M.,Hibbs, R.E.,Stowell, M.H.B.
Shape-shifting conotoxins reveal divergent pore-targeting mechanisms in nicotinic receptors.
Structure, 2025

PubMed Abstract: The neuronal α7 nicotinic acetylcholine receptor (α7-nAChR) and muscle-type nicotinic acetylcholine receptor (mt-nAChR) are pivotal in synaptic signaling within the brain and the neuromuscular junction respectively. Additionally, they are both targets of a wide range of drugs and toxins. Here, we utilize cryo-EM to delineate structures of these nAChRs in complex with the conotoxins ImI and ImII from Conus imperialis. Despite nominal sequence differences, ImI and ImII exhibit discrete binding preferences and adopt drastically different conformational states upon binding. ImI engages the orthosteric sites of α7-nAChR, while ImII forms distinct pore-bound complexes with both α7-nAChR and mt-nAChR. Strikingly, ImII adopts a compact globular conformation that binds as a monomer to the α7-nAChR pore and as an oblate dimer to the mt-nAChR pore. These structures advance our understanding of nAChR-ligand interactions and the subtle sequence variations that result in dramatically altered functional outcomes in small peptide toxins.

PubMed: 41468893
DOI: 10.1016/j.str.2025.12.003

Experimental method

ELECTRON MICROSCOPY (3.1 Å)