8vqc | pdb_00008vqc

Structure of the voltage-gated sodium channel NavPas from American Cockroach Periplaneta Americana in complex with scorpion alpha-toxin LqhaIT

spinqualitylabelsall models 8vqc, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8vqc is a 2 chain structure with sequence from Leiurus hebraeus and Periplaneta americana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SCNA1_PERAM Mediates the voltage-dependent sodium ion permeability of excitable membranes.[RuleBase:RU361132] Publication Abstract from PubMed Voltage-gated sodium (Nav) channels sense membrane potential and drive cellular electrical activity. The deathstalker scorpion alpha-toxin LqhalphaIT exerts a strong action potential prolonging effect on Nav channels. To elucidate the mechanism of action of LqhalphaIT, we determined a 3.9 A cryoelectron microscopy (cryo-EM) structure of LqhalphaIT in complex with the Nav channel from Periplaneta americana (NavPas). We found that LqhalphaIT binds to voltage sensor domain 4 and traps it in an "S4 down" conformation. The functionally essential C-terminal epitope of LqhalphaIT forms an extensive interface with the glycan scaffold linked to Asn330 of NavPas that augments a small protein-protein interface between NavPas and LqhalphaIT. A combination of molecular dynamics simulations, structural comparisons, and prior mutagenesis experiments demonstrates the functional importance of this toxin-glycan interaction. These findings establish a structural basis for the specificity achieved by scorpion alpha-toxins and reveal the conserved glycan as an essential component of the toxin-binding epitope. Scorpion alpha-toxin LqhalphaIT specifically interacts with a glycan at the pore domain of voltage-gated sodium channels.,Phulera S, Dickson CJ, Schwalen CJ, Khoshouei M, Cassell SJ, Sun Y, Condos T, Whicher J, Weihofen WA Structure. 2024 Aug 17:S0969-2126(24)00284-3. doi: 10.1016/j.str.2024.07.021. PMID:39181123 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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