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8J03

Human KCNQ2(F104A)-CaM-PIP2-CBD complex in state I

Summary for 8J03
Entry DOI10.2210/pdb8j03/pdb
EMDB information35882
DescriptorPotassium voltage-gated channel subfamily KQT member 2, Calmodulin-1, cannabidiol (3 entities in total)
Functional Keywordspotassium voltage-gated channel, cbd, pip2, membrane protein
Biological sourceHomo sapiens (human)
More
Total number of polymer chains8
Total formula weight373926.50
Authors
Ma, D.,Li, D.,Guo, J. (deposition date: 2023-04-09, release date: 2023-12-06)
Primary citationMa, D.,Zheng, Y.,Li, X.,Zhou, X.,Yang, Z.,Zhang, Y.,Wang, L.,Zhang, W.,Fang, J.,Zhao, G.,Hou, P.,Nan, F.,Yang, W.,Su, N.,Gao, Z.,Guo, J.
Ligand activation mechanisms of human KCNQ2 channel.
Nat Commun, 14:6632-6632, 2023
Cited by
PubMed Abstract: The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP, and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2.
PubMed: 37857637
DOI: 10.1038/s41467-023-42416-x
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.7 Å)
Structure validation

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