6AGF

Structure of the human voltage-gated sodium channel Nav1.4 in complex with beta1

Summary for 6AGF

• Entry DOI: 10.2210/pdb6agf/pdb
• EMDB information: 9617
• Descriptor: Sodium channel protein type 4 subunit alpha, Sodium channel subunit beta-1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: sodium channel, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 244299.03

Authors

Pan, X.J.,li, Z.Q.,Zhou, Q.,Shen, H.Z.,Wu, K.,Huang, X.S.,Chen, J.F.,Zhang, J.R.,Zhu, X.C.,Lei, J.L.,Xiong, W.,Gong, H.P.,Xiao, B.L.,Yan, N. (deposition date: 2018-08-11, release date: 2018-10-10, Last modification date: 2024-11-20)

Primary citation

Pan, X.,Li, Z.,Zhou, Q.,Shen, H.,Wu, K.,Huang, X.,Chen, J.,Zhang, J.,Zhu, X.,Lei, J.,Xiong, W.,Gong, H.,Xiao, B.,Yan, N.
Structure of the human voltage-gated sodium channel Nav1.4 in complex with beta 1.
Science, 362:-, 2018

PubMed Abstract: Voltage-gated sodium (Na) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Na channel has hampered mechanistic understanding. Here, we report the cryo-electron microscopy structure of the human Na1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, providing insight into the molecular basis for Na permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Na channels. The structure provides a path toward mechanistic investigation of Na channels and drug discovery for Na channelopathies.

PubMed: 30190309
DOI: 10.1126/science.aau2486

Experimental method

ELECTRON MICROSCOPY (3.2 Å)