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	Asymmetric gating of a homopentameric ion channel GLIC revealed by cryo-EM.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 122, Issue 43, Page e2512811122, Year 2025
掲載日	2025年10月28日
著者	Zhuowen Li / Nikhil Bharambe / Kashmiri Manishrao Lande / Bjarne Feddersen / Asha Manikkoth Balakrishna / Philip C Biggin / Giriraj Sahu / Sandip Basak /
PubMed 要旨	Pentameric ligand-gated ion channels (pLGICs) are vital neurotransmitter receptors that are key therapeutic targets for neurological disorders. Although the high-resolution structures of these ...Pentameric ligand-gated ion channels (pLGICs) are vital neurotransmitter receptors that are key therapeutic targets for neurological disorders. Although the high-resolution structures of these channels have been elucidated, capturing their dynamic conformational transitions remains challenging due to the transient nature of intermediate states. In this study, we investigated a prokaryotic proton-gated pLGIC, GLIC. In our cryo-EM data at pH 4.0, we identified and segregated asymmetric particles, which we precisely aligned to resolve high-resolution structures of several previously unresolved asymmetric intermediate states, in addition to symmetric closed and open states. Detailed structural analysis revealed systematic conformational changes at individual subunits driving the channel opening. Molecular dynamics simulations were used to assign the functional states. We further examined the roles of the F116 and Y251 residues, located at the domain interface, playing a central role in interdomain communication. In addition, patch-clamp experiments on GLIC I240A and L241A mutants, located in the M2 helix, demonstrated their importance in channel gating. Together, these results shed light on the sequential and asymmetric conformational transitions that occur during GLIC activation, offering a deeper mechanistic understanding of asymmetric gating in pLGICs.
リンク	Proc Natl Acad Sci U S A / PubMed:41129221 / PubMed Central
手法	EM (単粒子)
解像度	2.14 - 3.45 Å
構造データ	62927 9lag EMDB-62927, PDB-9lag: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC at pH 4 in iiiii conformation 手法: EM (単粒子) / 解像度: 2.96 Å 62929 9lai EMDB-62929, PDB-9lai: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC at pH 4 in iiiio conformation 手法: EM (単粒子) / 解像度: 3.08 Å 62930 9laj EMDB-62930, PDB-9laj: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC at pH 4 in iiioo conformation 手法: EM (単粒子) / 解像度: 3.16 Å 62931 9lak EMDB-62931, PDB-9lak: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC at pH 4 in iiooo conformation 手法: EM (単粒子) / 解像度: 3.21 Å 62937 9lb9 EMDB-62937, PDB-9lb9: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC at pH 4 in ioooo conformation 手法: EM (単粒子) / 解像度: 3.16 Å 62938 9lba EMDB-62938, PDB-9lba: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC at pH 4 in ooooo conformation 手法: EM (単粒子) / 解像度: 2.85 Å 62939 9lbb EMDB-62939, PDB-9lbb: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC at pH 4 in iioio conformation 手法: EM (単粒子) / 解像度: 3.45 Å 62940 9lbc EMDB-62940, PDB-9lbc: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC at pH 4 in ioioo conformation 手法: EM (単粒子) / 解像度: 3.4 Å 62941 9lbd EMDB-62941, PDB-9lbd: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC F116A mutant at pH 2.5 手法: EM (単粒子) / 解像度: 2.14 Å 62942 9lbe EMDB-62942, PDB-9lbe: Cryo-EM structure of nanodisc (PE:PS:PC) reconstituted GLIC Y251A mutant at pH 2.5 in ioooo conformation 手法: EM (単粒子) / 解像度: 2.87 Å
化合物	ChemComp-PEE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, リン脂質YM ChemComp-CL: Unknown entry ChemComp-HOH*: WATER
由来	gloeobacter violaceus (バクテリア)
キーワード	MEMBRANE PROTEIN / pentameric ligand-gated ion channels / cis-loop / cryo-EM / nanodisc