6A95

Complex of voltage-gated sodium channel NavPaS from American cockroach Periplaneta americana bound with tetrodotoxin and Dc1a

Summary for 6A95

• Entry DOI: 10.2210/pdb6a95/pdb
• EMDB information: 6997
• Descriptor: Sodium channel protein PaFPC1, Mu-diguetoxin-Dc1a, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: complex, sodium channel, toxin, membrane protein, membrane protein-toxin complex, membrane protein/toxin
• Biological source: Periplaneta americana (American cockroach); More
• Total number of polymer chains: 2
• Total formula weight: 192232.55

Authors

Shen, H.Z.,li, Z.Q.,Jiang, Y.,Pan, X.J.,Wu, J.P.,Cristofori-Armstrong, B.,Smith, J.J.,Chin, Y.K.Y.,Lei, J.L.,Zhou, Q.,King, G.F.,Yan, N. (deposition date: 2018-07-11, release date: 2018-08-08, Last modification date: 2024-11-13)

Primary citation

Shen, H.,Li, Z.,Jiang, Y.,Pan, X.,Wu, J.,Cristofori-Armstrong, B.,Smith, J.J.,Chin, Y.K.Y.,Lei, J.,Zhou, Q.,King, G.F.,Yan, N.
Structural basis for the modulation of voltage-gated sodium channels by animal toxins.
Science, 362:-, 2018

PubMed Abstract: Animal toxins that modulate the activity of voltage-gated sodium (Na) channels are broadly divided into two categories-pore blockers and gating modifiers. The pore blockers tetrodotoxin (TTX) and saxitoxin (STX) are responsible for puffer fish and shellfish poisoning in humans, respectively. Here, we present structures of the insect Na channel NaPaS bound to a gating modifier toxin Dc1a at 2.8 angstrom-resolution and in the presence of TTX or STX at 2.6-Å and 3.2-Å resolution, respectively. Dc1a inserts into the cleft between VSD and the pore of NaPaS, making key contacts with both domains. The structures with bound TTX or STX reveal the molecular details for the specific blockade of Na access to the selectivity filter from the extracellular side by these guanidinium toxins. The structures shed light on structure-based development of Na channel drugs.

PubMed: 30049784
DOI: 10.1126/science.aau2596

Experimental method

ELECTRON MICROSCOPY (2.6 Å)