- EMDB-22661: Structure of NavAb/Nav1.7-VS2A chimera trapped in the resting sta... -
+
Open data
ID or keywords:
Loading...
-
Basic information
Entry
Database: EMDB / ID: EMD-22661
Title
Structure of NavAb/Nav1.7-VS2A chimera trapped in the resting state by tarantula toxin m3-Huwentoxin-IV
Map data
EM map without post-cut-off B-factor sharpening
Sample
Complex: Complex of NavAb/Nav1.7-VS2A chimera and m3-Huwentoxin-IV
Complex: NavAb/Nav1.7-VS2A chimera
Protein or peptide: Maltose/maltodextrin-binding periplasmic protein,Ion transport protein,Sodium channel protein type 9 subunit alpha chimera
Complex: m3-Huwentoxin-IV
Protein or peptide: Mu-theraphotoxin-Hs2a
Function / homology
Function and homology information
detection of mechanical stimulus involved in sensory perception / host cell presynaptic membrane / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / membrane depolarization during action potential / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / ion channel inhibitor activity / sodium ion transport / detection of maltose stimulus ...detection of mechanical stimulus involved in sensory perception / host cell presynaptic membrane / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / membrane depolarization during action potential / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / ion channel inhibitor activity / sodium ion transport / detection of maltose stimulus / maltose transport complex / behavioral response to pain / Phase 0 - rapid depolarisation / carbohydrate transport / detection of temperature stimulus involved in sensory perception of pain / carbohydrate transmembrane transporter activity / maltose binding / sodium ion transmembrane transport / maltose transport / maltodextrin transmembrane transport / sodium channel regulator activity / neuronal action potential / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / sensory perception of pain / ATP-binding cassette (ABC) transporter complex / cell chemotaxis / post-embryonic development / response to toxic substance / Sensory perception of sweet, bitter, and umami (glutamate) taste / circadian rhythm / toxin activity / outer membrane-bounded periplasmic space / periplasmic space / inflammatory response / axon / DNA damage response / extracellular region / identical protein binding / membrane / metal ion binding / plasma membrane Similarity search - Function
Huwentoxin-1 family signature. / Huwentoxin, conserved site-1 / Huwentoxin-1 family / Ion channel inhibitory toxin / Voltage-gated Na+ ion channel, cytoplasmic domain / Cytoplasmic domain of voltage-gated Na+ ion channel / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / Sodium ion transport-associated / Voltage gated sodium channel, alpha subunit ...Huwentoxin-1 family signature. / Huwentoxin, conserved site-1 / Huwentoxin-1 family / Ion channel inhibitory toxin / Voltage-gated Na+ ion channel, cytoplasmic domain / Cytoplasmic domain of voltage-gated Na+ ion channel / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / Sodium ion transport-associated / Voltage gated sodium channel, alpha subunit / Voltage-gated cation channel calcium and sodium / Short calmodulin-binding motif containing conserved Ile and Gln residues. / IQ motif, EF-hand binding site / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Voltage-dependent channel domain superfamily / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein / Ion transport domain / Ion transport protein Similarity search - Domain/homology
Ion transport protein / Maltose/maltodextrin-binding periplasmic protein / Huwentoxin-IV / Sodium channel protein type 9 subunit alpha Similarity search - Component
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01 NS015751
United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)
R01 HL112808
United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R35 NS111573
United States
Howard Hughes Medical Institute (HHMI)
United States
Citation
Journal: Mol Cell / Year: 2021 Title: Structural Basis for High-Affinity Trapping of the Na1.7 Channel in Its Resting State by Tarantula Toxin. Authors: Goragot Wisedchaisri / Lige Tonggu / Tamer M Gamal El-Din / Eedann McCord / Ning Zheng / William A Catterall / Abstract: Voltage-gated sodium channels initiate electrical signals and are frequently targeted by deadly gating-modifier neurotoxins, including tarantula toxins, which trap the voltage sensor in its resting ...Voltage-gated sodium channels initiate electrical signals and are frequently targeted by deadly gating-modifier neurotoxins, including tarantula toxins, which trap the voltage sensor in its resting state. The structural basis for tarantula-toxin action remains elusive because of the difficulty of capturing the functionally relevant form of the toxin-channel complex. Here, we engineered the model sodium channel NaAb with voltage-shifting mutations and the toxin-binding site of human Na1.7, an attractive pain target. This mutant chimera enabled us to determine the cryoelectron microscopy (cryo-EM) structure of the channel functionally arrested by tarantula toxin. Our structure reveals a high-affinity resting-state-specific toxin-channel interaction between a key lysine residue that serves as a "stinger" and penetrates a triad of carboxyl groups in the S3-S4 linker of the voltage sensor. By unveiling this high-affinity binding mode, our studies establish a high-resolution channel-docking and resting-state locking mechanism for huwentoxin-IV and provide guidance for developing future resting-state-targeted analgesic drugs.
History
Deposition
Sep 15, 2020
-
Header (metadata) release
Dec 2, 2020
-
Map release
Dec 2, 2020
-
Update
Jan 20, 2021
-
Current status
Jan 20, 2021
Processing site: RCSB / Status: Released
-
Structure visualization
Movie
Surface view with section colored by density value
Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 12.0 nm / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 101.325 kPa
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV / Details: Blot for 2.5-4.0 seconds before plunging.
Details
m3-HwTx-IV was added in excess to the chimera at 8:1 stoichiometric molar ratio of toxin to channel.
-
Electron microscopy
Microscope
FEI TITAN KRIOS
Temperature
Min: 70.0 K / Max: 70.0 K
Specialist optics
Phase plate: VOLTA PHASE PLATE / Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Details
Preliminary grid screening was performed manually.
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 3710 pixel / Digitization - Dimensions - Height: 3582 pixel / Digitization - Frames/image: 2-42 / Number real images: 7168 / Average exposure time: 8.6 sec. / Average electron dose: 60.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)
EMDB accession codes are about to change! (news from PDBe EMDB page)
The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
The EM Navigator/Yorodumi systems omit the EMD- prefix.
Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator
Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.
Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi