Cav2.2 / Channels / Calcium Ion-Selective / TRANSPORT PROTEIN
機能・相同性
機能・相同性情報
positive regulation of high voltage-gated calcium channel activity / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / calcium ion transmembrane transport via high voltage-gated calcium channel / high voltage-gated calcium channel activity / membrane depolarization during bundle of His cell action potential / L-type voltage-gated calcium channel complex / NCAM1 interactions / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization ...positive regulation of high voltage-gated calcium channel activity / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / calcium ion transmembrane transport via high voltage-gated calcium channel / high voltage-gated calcium channel activity / membrane depolarization during bundle of His cell action potential / L-type voltage-gated calcium channel complex / NCAM1 interactions / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / calcium ion transport into cytosol / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / neuronal dense core vesicle / regulation of heart rate by cardiac conduction / response to amyloid-beta / calcium ion import across plasma membrane / regulation of calcium ion transport / voltage-gated calcium channel activity / presynaptic active zone membrane / calcium channel regulator activity / sarcoplasmic reticulum / protein localization to plasma membrane / GABA-ergic synapse / Regulation of insulin secretion / modulation of chemical synaptic transmission / cellular response to amyloid-beta / calcium ion transport / Adrenaline,noradrenaline inhibits insulin secretion / T cell receptor signaling pathway / amyloid-beta binding / chemical synaptic transmission / neuronal cell body / synapse / calcium ion binding / extracellular exosome / ATP binding / metal ion binding / membrane / plasma membrane / cytosol 類似検索 - 分子機能
Voltage-dependent calcium channel, N-type, alpha-1 subunit / Voltage-dependent calcium channel, L-type, beta-3 subunit / Voltage-dependent L-type calcium channel subunit beta-3, SH3 domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage gated calcium channel subunit beta domain 4Aa N terminal / VWA N-terminal / Voltage-dependent calcium channel, alpha-2/delta subunit, conserved region / VWA N-terminal / Neuronal voltage-dependent calcium channel alpha 2acd ...Voltage-dependent calcium channel, N-type, alpha-1 subunit / Voltage-dependent calcium channel, L-type, beta-3 subunit / Voltage-dependent L-type calcium channel subunit beta-3, SH3 domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage gated calcium channel subunit beta domain 4Aa N terminal / VWA N-terminal / Voltage-dependent calcium channel, alpha-2/delta subunit, conserved region / VWA N-terminal / Neuronal voltage-dependent calcium channel alpha 2acd / : / Voltage-dependent calcium channel, alpha-1 subunit, IQ domain / Voltage gated calcium channel IQ domain / Voltage gated calcium channel IQ domain / Voltage-dependent calcium channel, alpha-1 subunit / Voltage-dependent L-type calcium channel, IQ-associated domain / Voltage-dependent L-type calcium channel, IQ-associated / : / Guanylate kinase/L-type calcium channel beta subunit / Guanylate kinase / Guanylate kinase homologues. / von Willebrand factor type A domain / von Willebrand factor (vWF) type A domain / VWFA domain profile. / Voltage-dependent channel domain superfamily / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / EF-hand calcium-binding domain profile. / EF-hand domain / Ion transport domain / Ion transport protein / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
5R01GM130762
米国
引用
ジャーナル: Nature / 年: 2021 タイトル: Structure of human Ca2.2 channel blocked by the painkiller ziconotide. 著者: Shuai Gao / Xia Yao / Nieng Yan / 要旨: The neuronal-type (N-type) voltage-gated calcium (Ca) channels, which are designated Ca2.2, have an important role in the release of neurotransmitters. Ziconotide is a Ca2.2-specific peptide pore ...The neuronal-type (N-type) voltage-gated calcium (Ca) channels, which are designated Ca2.2, have an important role in the release of neurotransmitters. Ziconotide is a Ca2.2-specific peptide pore blocker that has been clinically used for treating intractable pain. Here we present cryo-electron microscopy structures of human Ca2.2 (comprising the core α1 and the ancillary α2δ-1 and β3 subunits) in the presence or absence of ziconotide. Ziconotide is thoroughly coordinated by helices P1 and P2, which support the selectivity filter, and the extracellular loops (ECLs) in repeats II, III and IV of α1. To accommodate ziconotide, the ECL of repeat III and α2δ-1 have to tilt upward concertedly. Three of the voltage-sensing domains (VSDs) are in a depolarized state, whereas the VSD of repeat II exhibits a down conformation that is stabilized by Ca2-unique intracellular segments and a phosphatidylinositol 4,5-bisphosphate molecule. Our studies reveal the molecular basis for Ca2.2-specific pore blocking by ziconotide and establish the framework for investigating electromechanical coupling in Ca channels.