Medicine and Health Sciences Commons^™

Conotoxin Αd-Gexxa Utilizes A Novel Strategy To Antagonize Nicotinic Acetylcholine Receptors, Shaoqiong Xu, Tianlong Zhang, Shiva N. Kompella, Mengdi Yan, Aiping Lu, Yanfang Wang, Xiaoxia Shao, Chengwu Chi, David J. Adams, Jianping Ding, Chunguang Wang

Illawarra Health and Medical Research Institute

Nicotinic acetylcholine receptors (nAChRs) play essential roles in transmitting acetylcholine-mediated neural signals across synapses and neuromuscular junctions, and are also closely linked to various diseases and clinical conditions. Therefore, novel nAChR-specific compounds have great potential for both neuroscience research and clinical applications. Conotoxins, the peptide neurotoxins produced by cone snails, are a rich reservoir of novel ligands that target receptors, ion channels and transporters in the nervous system. From the venom of Conus generalis, we identified a novel dimeric nAChR-inhibiting αD-conotoxin GeXXA. By solving the crystal structure and performing structure-guided dissection of this toxin, we demonstrated that the monomeric C-terminal …