8J7M

ion channel

Summary for 8J7M

• Entry DOI: 10.2210/pdb8j7m/pdb
• EMDB information: 36042
• Descriptor: ion channel,Voltage dependent ion channel,Green fluorescent protein (Fragment),Voltage dependent ion channel,Green fluorescent protein (Fragment),Voltage dependent ion channel,Green fluorescent protein (Fragment), (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, CHOLESTEROL (3 entities in total)
• Functional Keywords: ion channel, transport protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 367957.72

Authors

Chen, H.W.,Jiang, D. (deposition date: 2023-04-27, release date: 2024-05-15, Last modification date: 2025-01-15)

Primary citation

Chen, H.,Xia, Z.,Dong, J.,Huang, B.,Zhang, J.,Zhou, F.,Yan, R.,Shi, Y.,Gong, J.,Jiang, J.,Huang, Z.,Jiang, D.
Structural mechanism of voltage-gated sodium channel slow inactivation.
Nat Commun, 15:3691-3691, 2024

PubMed Abstract: Voltage-gated sodium (Na) channels mediate a plethora of electrical activities. Na channels govern cellular excitability in response to depolarizing stimuli. Inactivation is an intrinsic property of Na channels that regulates cellular excitability by controlling the channel availability. The fast inactivation, mediated by the Ile-Phe-Met (IFM) motif and the N-terminal helix (N-helix), has been well-characterized. However, the molecular mechanism underlying Na channel slow inactivation remains elusive. Here, we demonstrate that the removal of the N-helix of NaEh (NaEh) results in a slow-inactivated channel, and present cryo-EM structure of NaEh in a potential slow-inactivated state. The structure features a closed activation gate and a dilated selectivity filter (SF), indicating that the upper SF and the inner gate could serve as a gate for slow inactivation. In comparison to the NaEh structure, NaEh undergoes marked conformational shifts on the intracellular side. Together, our results provide important mechanistic insights into Na channel slow inactivation.

PubMed: 38693179
DOI: 10.1038/s41467-024-48125-3

Experimental method

ELECTRON MICROSCOPY (3.1 Å)