|Entry||Database: PDB / ID: 6j8h|
|Title||Structure of human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits, huwentoxin-IV and saxitoxin (Y1755 down)|
|Keywords||MEMBRANE PROTEIN / voltage-gated sodium channel|
|Function / homology||Sodium ion transport-associated / Voltage-dependent channel domain superfamily / IQ motif, EF-hand binding site / Myelin P0 protein-related / Voltage gated sodium channel, alpha subunit / Immunoglobulin subtype / Ion transport domain / Immunoglobulin-like domain / Immunoglobulin V-set domain / Immunoglobulin-like fold ...Sodium ion transport-associated / Voltage-dependent channel domain superfamily / IQ motif, EF-hand binding site / Myelin P0 protein-related / Voltage gated sodium channel, alpha subunit / Immunoglobulin subtype / Ion transport domain / Immunoglobulin-like domain / Immunoglobulin V-set domain / Immunoglobulin-like fold / Voltage-gated Na+ ion channel, cytoplasmic domain / Sodium channel subunit beta-1/beta-3 / Voltage gated sodium channel, alpha-9 subunit / Sodium channel subunit beta-2 / Immunoglobulin-like domain superfamily / Ion transport protein / Sodium ion transport-associated / Immunoglobulin V-set domain / Cytoplasmic domain of voltage-gated Na+ ion channel / Ig-like domain profile. / Interaction between L1 and Ankyrins / Phase 0 - rapid depolarisation / corticospinal neuron axon guidance / regulation of voltage-gated sodium channel activity / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / response to pyrethroid / regulation of atrial cardiac muscle cell membrane depolarization / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / locomotion / cardiac conduction / regulation of sodium ion transmembrane transporter activity / membrane depolarization during cardiac muscle cell action potential / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / membrane depolarization during action potential / regulation of ventricular cardiac muscle cell membrane repolarization / behavioral response to pain / node of Ranvier / neuronal action potential propagation / positive regulation of sodium ion transport / voltage-gated sodium channel activity / sodium channel inhibitor activity / sodium ion binding / neuronal action potential / sodium ion transmembrane transport / regulation of heart rate by cardiac conduction / sodium ion transport / voltage-gated ion channel activity / membrane depolarization / intercalated disc / regulation of ion transmembrane transport / T-tubule / cardiac muscle contraction / sodium channel regulator activity / sensory perception of pain / post-embryonic development / positive regulation of neuron projection development / response to toxic substance / nervous system development / axon guidance / chemical synaptic transmission / ion channel binding / cell adhesion / inflammatory response / axon / integral component of plasma membrane / extracellular region / plasma membrane / Sodium channel subunit beta-2 / Sodium channel subunit beta-1 / Sodium channel protein type 9 subunit alpha|
Function and homology information
|Specimen source||Homo sapiens (human)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 3.2 Å resolution|
|Authors||Shen, H. / Liu, D. / Lei, J. / Yan, N.|
|Funding support||China , 5 items |
|Citation||Journal: Science / Year: 2019|
Title: Structures of human Na1.7 channel in complex with auxiliary subunits and animal toxins.
Authors: Huaizong Shen / Dongliang Liu / Kun Wu / Jianlin Lei / Nieng Yan
Abstract: Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na1.7-β1-β2 complex bound to two combinations ...Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na1.7-β1-β2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with protoxin-II and saxitoxin with huwentoxin-IV, both determined at overall resolutions of 3.2 angstroms. The two structures are nearly identical except for minor shifts of voltage-sensing domain II (VSD), whose S3-S4 linker accommodates the two GMTs in a similar manner. One additional protoxin-II sits on top of the S3-S4 linker in VSD The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. The structures illuminate the path toward mechanistic understanding of the function and disease of Na1.7 and establish the foundation for structure-aided development of analgesics.
SummaryFull reportAbout validation report
|Date||Deposition: Jan 19, 2019 / Release: Feb 27, 2019|
|Structure viewer||Molecule: |
Downloads & links
C: Sodium channel subunit beta-2
A: Sodium channel protein type 9 subunit alpha
B: Sodium channel subunit beta-1
|#1: Protein/peptide|| |
Mass: 24355.859 Da / Num. of mol.: 1 / Source: (gene. exp.) Homo sapiens (human) / Gene: SCN2B, UNQ326/PRO386 / Production host: Homo sapiens (human) / References: UniProt: O60939
|#2: Protein/peptide|| |
Mass: 231211.922 Da / Num. of mol.: 1 / Source: (gene. exp.) Homo sapiens (human) / Gene: SCN9A, NENA / Production host: Homo sapiens (human) / References: UniProt: Q15858
|#3: Protein/peptide|| |
Mass: 24732.115 Da / Num. of mol.: 1 / Source: (gene. exp.) Homo sapiens (human) / Gene: SCN1B / Production host: Homo sapiens (human) / References: UniProt: Q07699
|#5: Chemical|| ChemComp-9SL / [(|
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: single particle reconstruction|
|Component||Name: Complex of human voltage-gated sodium channel Nav1.7 with auxiliary beta subunits, huwentoxin-IV and saxitoxin|
Type: COMPLEX / Entity ID: 1,
|Source (natural)||Organism: Homo sapiens (human)||Source (recombinant)||Organism: Homo sapiens (human)||Buffer solution||pH: 7.4||Specimen||Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES||Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy|
|Image recording||Electron dose: 48 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k)|
|Software||Name: PHENIX / Version: 1.11.1_2575: / Classification: refinement|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|3D reconstruction||Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 275630 / Symmetry type: POINT|
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