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 / behavioral response to pain ...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 / behavioral response to pain / Phase 0 - rapid depolarisation / detection of temperature stimulus involved in sensory perception of pain / sodium ion transmembrane transport / sodium channel regulator activity / neuronal action potential / sensory perception of pain / post-embryonic development / response to toxic substance / Sensory perception of sweet, bitter, and umami (glutamate) taste / circadian rhythm / toxin activity / inflammatory response / axon / extracellular region / plasma membrane 類似検索 - 分子機能
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 / Voltage-dependent channel domain superfamily / Ion transport domain / Ion transport protein 類似検索 - ドメイン・相同性
Huwentoxin-IV / Sodium channel protein type 9 subunit alpha / BH1501 protein 類似検索 - 構成要素
ジャーナル: Proc Natl Acad Sci U S A / 年: 2020 タイトル: Employing NaChBac for cryo-EM analysis of toxin action on voltage-gated Na channels in nanodisc. 著者: Shuai Gao / William C Valinsky / Nguyen Cam On / Patrick R Houlihan / Qian Qu / Lei Liu / Xiaojing Pan / David E Clapham / Nieng Yan / 要旨: NaChBac, the first bacterial voltage-gated Na (Na) channel to be characterized, has been the prokaryotic prototype for studying the structure-function relationship of Na channels. Discovered nearly ...NaChBac, the first bacterial voltage-gated Na (Na) channel to be characterized, has been the prokaryotic prototype for studying the structure-function relationship of Na channels. Discovered nearly two decades ago, the structure of NaChBac has not been determined. Here we present the single particle electron cryomicroscopy (cryo-EM) analysis of NaChBac in both detergent micelles and nanodiscs. Under both conditions, the conformation of NaChBac is nearly identical to that of the potentially inactivated NaAb. Determining the structure of NaChBac in nanodiscs enabled us to examine gating modifier toxins (GMTs) of Na channels in lipid bilayers. To study GMTs in mammalian Na channels, we generated a chimera in which the extracellular fragment of the S3 and S4 segments in the second voltage-sensing domain from Na1.7 replaced the corresponding sequence in NaChBac. Cryo-EM structures of the nanodisc-embedded chimera alone and in complex with HuwenToxin IV (HWTX-IV) were determined to 3.5 and 3.2 Å resolutions, respectively. Compared to the structure of HWTX-IV-bound human Na1.7, which was obtained at an overall resolution of 3.2 Å, the local resolution of the toxin has been improved from ∼6 to ∼4 Å. This resolution enabled visualization of toxin docking. NaChBac can thus serve as a convenient surrogate for structural studies of the interactions between GMTs and Na channels in a membrane environment.