8XMM

Voltage-gated sodium channel Nav1.7 variant M9

Summary for 8XMM

• Entry DOI: 10.2210/pdb8xmm/pdb
• EMDB information: 38482
• Descriptor: Sodium channel protein type 9 subunit alpha, Sodium channel subunit beta-1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: voltage-gated sodium channel, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 271023.51

Authors

Yan, N.,Li, Z.,Wu, Q.,Huang, G. (deposition date: 2023-12-27, release date: 2024-03-06, Last modification date: 2024-10-09)

Primary citation

Li, Z.,Wu, Q.,Huang, G.,Jin, X.,Li, J.,Pan, X.,Yan, N.
Dissection of the structure-function relationship of Na v channels.
Proc.Natl.Acad.Sci.USA, 121:e2322899121-e2322899121, 2024

PubMed Abstract: Voltage-gated sodium channels (Na) undergo conformational shifts in response to membrane potential changes, a mechanism known as the electromechanical coupling. To delineate the structure-function relationship of human Na channels, we have performed systematic structural analysis using human Na1.7 as a prototype. Guided by the structural differences between wild-type (WT) Na1.7 and an eleven mutation-containing variant, designated Na1.7-M11, we generated three additional intermediate mutants and solved their structures at overall resolutions of 2.9-3.4 Å. The mutant with nine-point mutations in the pore domain (PD), named Na1.7-M9, has a reduced cavity volume and a sealed gate, with all voltage-sensing domains (VSDs) remaining up. Structural comparison of WT and Na1.7-M9 pinpoints two residues that may be critical to the tightening of the PD. However, the variant containing these two mutations, Na1.7-M2, or even in combination with two additional mutations in the VSDs, named Na1.7-M4, failed to tighten the PD. Our structural analysis reveals a tendency of PD contraction correlated with the right shift of the static inactivation I-V curves. We predict that the channel in the resting state should have a "tight" PD with down VSDs.

PubMed: 38381792
DOI: 10.1073/pnas.2322899121

Experimental method

ELECTRON MICROSCOPY (2.89 Å)