7W9L
Cryo-EM structure of human Nav1.7(E406K)-beta1-beta2 complex
Summary for 7W9L
Entry DOI | 10.2210/pdb7w9l/pdb |
EMDB information | 32369 |
Descriptor | Sodium channel protein type 9 subunit alpha, 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, Sodium channel subunit beta-1, ... (10 entities in total) |
Functional Keywords | nav1.7, scn9a, cryo-em, membrane protein |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 3 |
Total formula weight | 299606.04 |
Authors | |
Primary citation | Huang, G.,Liu, D.,Wang, W.,Wu, Q.,Chen, J.,Pan, X.,Shen, H.,Yan, N. High-resolution structures of human Na v 1.7 reveal gating modulation through alpha-pi helical transition of S6 IV. Cell Rep, 39:110735-110735, 2022 Cited by PubMed Abstract: Na1.7 represents a preeminent target for next-generation analgesics for its critical role in pain sensation. Here we report a 2.2-Å resolution cryo-EM structure of wild-type (WT) Na1.7 complexed with the β1 and β2 subunits that reveals several previously indiscernible cytosolic segments. Reprocessing of the cryo-EM data for our reported structures of Na1.7(E406K) bound to various toxins identifies two distinct conformations of S6, one composed of α helical turns only and the other containing a π helical turn in the middle. The structure of ligand-free Na1.7(E406K), determined at 3.5-Å resolution, is identical to the WT channel, confirming that binding of Huwentoxin IV or Protoxin II to VSD allosterically induces the α → π transition of S6. The local secondary structural shift leads to contraction of the intracellular gate, closure of the fenestration on the interface of repeats I and IV, and rearrangement of the binding site for the fast inactivation motif. PubMed: 35476982DOI: 10.1016/j.celrep.2022.110735 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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