43SN

Alpha-7 nicotinic acetylcholine receptor bound to inhibitory bicyclic peptide KP1877 in a resting state

Summary for 43SN

• Entry DOI: 10.2210/pdb43sn/pdb
• Related: 9LN7
• EMDB information: 82114
• Descriptor: Neuronal acetylcholine receptor subunit alpha-7, synthetic peptide KP1877, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: nicotinic acetylcholine receptor, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 296170.49

Authors

Chen, H.,Sun, D.,Tian, C. (deposition date: 2026-07-15, release date: 2026-08-26)

Primary citation

Yang, X.,Cui, K.,Cao, X.,Chen, H.,Tian, C.,Sun, D.
Screening, synthesis and structural characterization of a novel bicyclic peptide inhibiting alpha 7 nicotinic acetylcholine receptor.
Chem.Commun.(Camb.), 2026

PubMed Abstract: Peptides targeting the α7 nicotinic acetylcholine receptor (α7-nAChR) represent promising candidates for therapeutic and chemical probe development. Here, we identified a novel bicyclic peptide KP1877 phage-displayed peptide library screening followed by chemical synthesis of active analogs. Structural characterization reveals KP1877 adopts a unique bicyclic conformation distinct from known natural α7-nAChR-targeting peptides, and exerts potent inhibitory effect by stabilizing the closed, non-conducting state of the receptor orthosteric binding.

PubMed: 42574057
DOI: 10.1039/d6cc03853k

Experimental method

ELECTRON MICROSCOPY (2.71 Å)