6MWA

NavAb Voltage-gated Sodium Channel, residues 1-239

Summary for 6MWA

• Entry DOI: 10.2210/pdb6mwa/pdb
• Descriptor: Ion transport protein, 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: ion channel voltage-gated sodium channel, membrane protein, metal transport
• Biological source: Arcobacter butzleri (strain RM4018)
• Total number of polymer chains: 1
• Total formula weight: 33830.87

Authors

Lenaeus, M.J.,Catterall, W.A. (deposition date: 2018-10-29, release date: 2018-12-19, Last modification date: 2023-10-11)

Primary citation

Gamal El-Din, T.M.,Lenaeus, M.J.,Ramanadane, K.,Zheng, N.,Catterall, W.A.
Molecular dissection of multiphase inactivation of the bacterial sodium channel NaVAb.
J. Gen. Physiol., 151:174-185, 2019

PubMed Abstract: Homotetrameric bacterial voltage-gated sodium channels share major biophysical features with their more complex eukaryotic counterparts, including a slow-inactivation mechanism that reduces ion-conductance activity during prolonged depolarization through conformational changes in the pore. The bacterial sodium channel NaAb activates at very negative membrane potentials and inactivates through a multiphase slow-inactivation mechanism. Early voltage-dependent inactivation during one depolarization is followed by late use-dependent inactivation during repetitive depolarization. Mutations that change the molecular volume of Thr206 in the pore-lining S6 segment can enhance or strongly block early voltage-dependent inactivation, suggesting that this residue serves as a molecular hub controlling the coupling of activation to inactivation. In contrast, truncation of the C-terminal tail enhances the early phase of inactivation yet completely blocks late use-dependent inactivation. Determination of the structure of a C-terminal tail truncation mutant and molecular modeling of conformational changes at Thr206 and the S6 activation gate led to a two-step model of these gating processes. First, bending of the S6 segment, local protein interactions dependent on the size of Thr206, and exchange of hydrogen-bonding partners at the level of Thr206 trigger pore opening followed by the early phase of voltage-dependent inactivation. Thereafter, conformational changes in the C-terminal tail lead to late use-dependent inactivation. These results have important implications for the sequence of conformational changes that lead to multiphase inactivation of NaAb and other sodium channels.

PubMed: 30510035
DOI: 10.1085/jgp.201711884

Experimental method

X-RAY DIFFRACTION (2.4 Å)