Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2017 Mar 07;11410:E1857-E1865. doi: 10.1073/pnas.1700453114.
Show Gene links
Show Anatomy links
Mapping of voltage sensor positions in resting and inactivated mammalian sodium channels by LRET.
Kubota T
,
Durek T
,
Dang B
,
Finol-Urdaneta RK
,
Craik DJ
,
Kent SB
,
French RJ
,
Bezanilla F
,
Correa AM
.
???displayArticle.abstract???
Voltage-gated sodium channels (Navs) play crucial roles in excitable cells. Although vertebrate Nav function has been extensively studied, the detailed structural basis for voltage-dependent gating mechanisms remain obscure. We have assessed the structural changes of the Nav voltage sensor domain using lanthanide-based resonance energy transfer (LRET) between the rat skeletal muscle voltage-gated sodium channel (Nav1.4) and fluorescently labeled Nav1.4-targeting toxins. We generated donor constructs with genetically encoded lanthanide-binding tags (LBTs) inserted at the extracellular end of the S4 segment of each domain (with a single LBT per construct). Three different Bodipy-labeled, Nav1.4-targeting toxins were synthesized as acceptors: β-scorpion toxin (Ts1)-Bodipy, KIIIA-Bodipy, and GIIIA-Bodipy analogs. Functional Nav-LBT channels expressed in Xenopus oocytes were voltage-clamped, and distinct LRET signals were obtained in the resting and slow inactivated states. Intramolecular distances computed from the LRET signals define a geometrical map of Nav1.4 with the bound toxins, and reveal voltage-dependent structural changes related to channel gating.
Bezanilla,
Distribution and kinetics of membrane dielectric polarization. 1. Long-term inactivation of gating currents.
1982, Pubmed
Bezanilla,
Distribution and kinetics of membrane dielectric polarization. 1. Long-term inactivation of gating currents.
1982,
Pubmed
Campos,
beta-Scorpion toxin modifies gating transitions in all four voltage sensors of the sodium channel.
2007,
Pubmed
,
Xenbase
Capes,
Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.
2012,
Pubmed
Capes,
Domain IV voltage-sensor movement is both sufficient and rate limiting for fast inactivation in sodium channels.
2013,
Pubmed
,
Xenbase
Cestèle,
Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II.
1998,
Pubmed
Chanda,
Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation.
2002,
Pubmed
,
Xenbase
Cruz,
mu-conotoxin GIIIA, a peptide ligand for muscle sodium channels: chemical synthesis, radiolabeling, and receptor characterization.
1989,
Pubmed
Dang,
Total chemical synthesis of biologically active fluorescent dye-labeled Ts1 toxin.
2014,
Pubmed
French,
The tetrodotoxin receptor of voltage-gated sodium channels--perspectives from interactions with micro-conotoxins.
2010,
Pubmed
French,
Interactions between a pore-blocking peptide and the voltage sensor of the sodium channel: an electrostatic approach to channel geometry.
1996,
Pubmed
Goldschen-Ohm,
Multiple pore conformations driven by asynchronous movements of voltage sensors in a eukaryotic sodium channel.
2013,
Pubmed
,
Xenbase
HODGKIN,
A quantitative description of membrane current and its application to conduction and excitation in nerve.
1952,
Pubmed
Hui,
Electrostatic and steric contributions to block of the skeletal muscle sodium channel by mu-conotoxin.
2002,
Pubmed
Hyde,
Nano-positioning system for structural analysis of functional homomeric proteins in multiple conformations.
2012,
Pubmed
,
Xenbase
Khoo,
Distinct disulfide isomers of μ-conotoxins KIIIA and KIIIB block voltage-gated sodium channels.
2012,
Pubmed
Korkosh,
Folding similarity of the outer pore region in prokaryotic and eukaryotic sodium channels revealed by docking of conotoxins GIIIA, PIIIA, and KIIIA in a NavAb-based model of Nav1.4.
2014,
Pubmed
Kubota,
Probing α-3(10) transitions in a voltage-sensing S4 helix.
2014,
Pubmed
,
Xenbase
Lacroix,
Molecular bases for the asynchronous activation of sodium and potassium channels required for nerve impulse generation.
2013,
Pubmed
,
Xenbase
Lacroix,
Properties of deactivation gating currents in Shaker channels.
2011,
Pubmed
Lancelin,
Tertiary structure of conotoxin GIIIA in aqueous solution.
1991,
Pubmed
Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed
McArthur,
Interactions of key charged residues contributing to selective block of neuronal sodium channels by μ-conotoxin KIIIA.
2011,
Pubmed
McCusker,
Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing.
2012,
Pubmed
Nitz,
Structural origin of the high affinity of a chemically evolved lanthanide-binding peptide.
2004,
Pubmed
Pantazis,
Functional heterogeneity of the four voltage sensors of a human L-type calcium channel.
2014,
Pubmed
Payandeh,
Crystal structure of a voltage-gated sodium channel in two potentially inactivated states.
2012,
Pubmed
Payandeh,
The crystal structure of a voltage-gated sodium channel.
2011,
Pubmed
Possani,
Scorpion toxins specific for Na+-channels.
1999,
Pubmed
Posson,
Extent of voltage sensor movement during gating of shaker K+ channels.
2008,
Pubmed
,
Xenbase
Posson,
Small vertical movement of a K+ channel voltage sensor measured with luminescence energy transfer.
2005,
Pubmed
,
Xenbase
Sandtner,
In vivo measurement of intramolecular distances using genetically encoded reporters.
2007,
Pubmed
,
Xenbase
Selvin,
Principles and biophysical applications of lanthanide-based probes.
2002,
Pubmed
Stefani,
Cut-open oocyte voltage-clamp technique.
1998,
Pubmed
,
Xenbase
Vargas,
An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations.
2012,
Pubmed
Vargas,
In search of a consensus model of the resting state of a voltage-sensing domain.
2011,
Pubmed
Villalba-Galea,
S4-based voltage sensors have three major conformations.
2008,
Pubmed
Wu,
Structure of the voltage-gated calcium channel Cav1.1 complex.
2015,
Pubmed
Wu,
Structure of the voltage-gated calcium channel Ca(v)1.1 at 3.6 Å resolution.
2016,
Pubmed
Zhang,
Structure-function map of the receptor site for β-scorpion toxins in domain II of voltage-gated sodium channels.
2011,
Pubmed
Zhang,
Mapping the interaction site for a β-scorpion toxin in the pore module of domain III of voltage-gated Na(+) channels.
2012,
Pubmed
Zhang,
Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels.
2007,
Pubmed
,
Xenbase
Zhang,
Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel.
2012,
Pubmed
