EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Ball-and-chain inactivation in a calcium-gated potassium channel.
ジャーナル・号・ページ	Nature, Vol. 580, Issue 7802, Page 288-293, Year 2020
掲載日	2020年3月18日
著者	Chen Fan / Nattakan Sukomon / Emelie Flood / Jan Rheinberger / Toby W Allen / Crina M Nimigean /
PubMed 要旨	Inactivation is the process by which ion channels terminate ion flux through their pores while the opening stimulus is still present. In neurons, inactivation of both sodium and potassium channels is ...Inactivation is the process by which ion channels terminate ion flux through their pores while the opening stimulus is still present. In neurons, inactivation of both sodium and potassium channels is crucial for the generation of action potentials and regulation of firing frequency. A cytoplasmic domain of either the channel or an accessory subunit is thought to plug the open pore to inactivate the channel via a 'ball-and-chain' mechanism. Here we use cryo-electron microscopy to identify the molecular gating mechanism in calcium-activated potassium channels by obtaining structures of the MthK channel from Methanobacterium thermoautotrophicum-a purely calcium-gated and inactivating channel-in a lipid environment. In the absence of Ca, we obtained a single structure in a closed state, which was shown by atomistic simulations to be highly flexible in lipid bilayers at ambient temperature, with large rocking motions of the gating ring and bending of pore-lining helices. In Ca-bound conditions, we obtained several structures, including multiple open-inactivated conformations, further indication of a highly dynamic protein. These different channel conformations are distinguished by rocking of the gating rings with respect to the transmembrane region, indicating symmetry breakage across the channel. Furthermore, in all conformations displaying open channel pores, the N terminus of one subunit of the channel tetramer sticks into the pore and plugs it, with free energy simulations showing that this is a strong interaction. Deletion of this N terminus leads to functionally non-inactivating channels and structures of open states without a pore plug, indicating that this previously unresolved N-terminal peptide is responsible for a ball-and-chain inactivation mechanism.
リンク	Nature / PubMed:32269335 / PubMed Central
手法	EM (単粒子)
解像度	3.2 - 6.7 Å
構造データ	20650 6u5n EMDB-20650, PDB-6u5n: Calcium-bound MthK gating ring state 2 手法: EM (単粒子) / 解像度: 3.2 Å 20652 6u5p EMDB-20652, PDB-6u5p: Calcium-bound MthK gating ring state 1 手法: EM (単粒子) / 解像度: 3.3 Å 20653 6u5r EMDB-20653, PDB-6u5r: Calcium-bound MthK closed state 手法: EM (単粒子) / 解像度: 3.6 Å 20662 6u68 EMDB-20662, PDB-6u68: Calcium-bound MthK open-inactivated state 1 手法: EM (単粒子) / 解像度: 4.5 Å 20663 6u6d EMDB-20663, PDB-6u6d: MthK closed state with EDTA 手法: EM (単粒子) / 解像度: 3.6 Å 20664 6u6e EMDB-20664, PDB-6u6e: Calcium-bound MthK open-inactivated state 2 手法: EM (単粒子) / 解像度: 6.3 Å 20665 6u6h EMDB-20665, PDB-6u6h: Calcium-bound MthK open-inactivated state 3 手法: EM (単粒子) / 解像度: 5.0 Å 20925 6uwn EMDB-20925, PDB-6uwn: MthK N-terminal truncation RCK domain state 1 bound with calcium 手法: EM (単粒子) / 解像度: 3.5 Å 20929 6ux4 EMDB-20929, PDB-6ux4: MthK N-terminal truncation RCK domain state 2 bound with calcium 手法: EM (単粒子) / 解像度: 3.5 Å 20930 6ux7 EMDB-20930, PDB-6ux7: MthK N-terminal truncation state 1 bound with calcium 手法: EM (単粒子) / 解像度: 6.7 Å 20931 6uxa EMDB-20931, PDB-6uxa: MthK N-terminal truncation state 2 bound with calcium 手法: EM (単粒子) / 解像度: 4.5 Å 20932 6uxb EMDB-20932, PDB-6uxb: MthK N-terminal truncation state 3 bound with calcium 手法: EM (単粒子) / 解像度: 4.9 Å
化合物	ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-HOH: WATER ChemComp-K: Unknown entry / カリウムカチオン
由来	methanothermobacter thermautotrophicus (古細菌)
キーワード	TRANSPORT PROTEIN / MthK / inactivation