9LJ1

Human KCNQ5-CaM-PIP2-HN37 complex in a closed conformation.

Summary for 9LJ1

• Entry DOI: 10.2210/pdb9lj1/pdb
• EMDB information: 63130
• Descriptor: Potassium voltage-gated channel subfamily KQT member 5, Calmodulin-3, methyl N-[4-[(4-fluorophenyl)methyl-prop-2-ynyl-amino]-2,6-dimethyl-phenyl]carbamate, ... (4 entities in total)
• Functional Keywords: voltage-gated potassium channel, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 364662.76

Authors

Yang, Z.,Guo, J. (deposition date: 2025-01-14, release date: 2025-04-16, Last modification date: 2025-05-14)

Primary citation

Yang, Z.,Zheng, Y.,Ma, D.,Wang, L.,Zhang, J.,Song, T.,Wang, Y.,Zhang, Y.,Nan, F.,Su, N.,Gao, Z.,Guo, J.
Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5.
Proc.Natl.Acad.Sci.USA, 122:e2416738122-e2416738122, 2025

PubMed Abstract: The human voltage-gated potassium channels KCNQ2, KCNQ3, and KCNQ5 can form homo- and heterotetrameric channels that are responsible for generating the neuronal M current and maintaining the membrane potential stable. Activation of KCNQ channels requires both the depolarization of membrane potential and phosphatidylinositol 4,5-bisphosphate (PIP). Here, we report cryoelectron microscopy structures of the human KCNQ5-calmodulin (CaM) complex in the apo, PIP-bound, and both PIP- and the activator HN37-bound states in either a closed or an open conformation. In the closed conformation, a PIP molecule binds in the middle of the groove between two adjacent voltage-sensing domains (VSDs), whereas in the open conformation, one additional PIP binds to the interface of VSD and the pore domain, accompanying structural rearrangement of the cytosolic domain of KCNQ and CaM. The structures, along with electrophysiology analyses, reveal the two different binding modes of PIP and elucidate the PIP activation mechanism of KCNQ5.

PubMed: 40172963
DOI: 10.1073/pnas.2416738122

Experimental method

ELECTRON MICROSCOPY (3.2 Å)