3RVZ

Crystal structure of the NavAb voltage-gated sodium channel (Ile217Cys, 2.8 A)

Summary for 3RVZ

• Entry DOI: 10.2210/pdb3rvz/pdb
• Related: 3RVY 3RW0
• Descriptor: Ion transport protein, 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total)
• Functional Keywords: tetrameric ion channel, voltage-gated sodium-selective ion channel, membrane, metal transport
• Biological source: Arcobacter butzleri
• Total number of polymer chains: 2
• Total formula weight: 75715.35

Authors

Payandeh, J.,Scheuer, T.,Zheng, N.,Catterall, W.A. (deposition date: 2011-05-06, release date: 2011-07-13, Last modification date: 2024-04-03)

Primary citation

Payandeh, J.,Scheuer, T.,Zheng, N.,Catterall, W.A.
The crystal structure of a voltage-gated sodium channel.
Nature, 475:353-358, 2011

PubMed Abstract: Voltage-gated sodium (Na(V)) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs and disease mutations, but the structural basis for their voltage-dependent activation, ion selectivity and drug block is unknown. Here we report the crystal structure of a voltage-gated Na(+) channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors at 2.7 Å resolution. The arginine gating charges make multiple hydrophilic interactions within the voltage sensor, including unanticipated hydrogen bonds to the protein backbone. Comparisons to previous open-pore potassium channel structures indicate that the voltage-sensor domains and the S4-S5 linkers dilate the central pore by pivoting together around a hinge at the base of the pore module. The NavAb selectivity filter is short, ∼4.6 Å wide, and water filled, with four acidic side chains surrounding the narrowest part of the ion conduction pathway. This unique structure presents a high-field-strength anionic coordination site, which confers Na(+) selectivity through partial dehydration via direct interaction with glutamate side chains. Fenestrations in the sides of the pore module are unexpectedly penetrated by fatty acyl chains that extend into the central cavity, and these portals are large enough for the entry of small, hydrophobic pore-blocking drugs. This structure provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level.

PubMed: 21743477
DOI: 10.1038/nature10238

Experimental method

X-RAY DIFFRACTION (2.8 Å)