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	Allosteric modulation of LRRC8 channels by targeting their cytoplasmic domains.
ジャーナル・号・ページ	Nat Commun, Vol. 12, Issue 1, Page 5435, Year 2021
掲載日	2021年9月14日
著者	Dawid Deneka / Sonja Rutz / Cedric A J Hutter / Markus A Seeger / Marta Sawicka / Raimund Dutzler /
PubMed 要旨	Members of the LRRC8 family form heteromeric assemblies, which function as volume-regulated anion channels. These modular proteins consist of a transmembrane pore and cytoplasmic leucine-rich repeat ...Members of the LRRC8 family form heteromeric assemblies, which function as volume-regulated anion channels. These modular proteins consist of a transmembrane pore and cytoplasmic leucine-rich repeat (LRR) domains. Despite their known molecular architecture, the mechanism of activation and the role of the LRR domains in this process has remained elusive. Here we address this question by generating synthetic nanobodies, termed sybodies, which target the LRR domain of the obligatory subunit LRRC8A. We use these binders to investigate their interaction with homomeric LRRC8A channels by cryo-electron microscopy and the consequent effect on channel activation by electrophysiology. The five identified sybodies either inhibit or enhance activity by binding to distinct epitopes of the LRR domain, thereby altering channel conformations. In combination, our work provides a set of specific modulators of LRRC8 proteins and reveals the role of their cytoplasmic domains as regulators of channel activity by allosteric mechanisms.
リンク	Nat Commun / PubMed:34521847 / PubMed Central
手法	EM (単粒子)
解像度	3.06 - 7.67 Å
構造データ	13202 7p5v EMDB-13202: Cryo-EM structure of homomeric LRRC8A Volume-Regulated Anion Channel in complex with synthetic nanobody Sb1 PDB-7p5v: Structure of homomeric LRRC8A Volume-Regulated Anion Channel in complex with synthetic nanobody Sb1 手法: EM (単粒子) / 解像度: 3.06 Å 13203 7p5w EMDB-13203: Cryo-EM structure of homomeric LRRC8A Volume-Regulated Anion Channel in complex with synthetic nanobody Sb2 PDB-7p5w: Structure of homomeric LRRC8A Volume-Regulated Anion Channel in complex with synthetic nanobody Sb2 手法: EM (単粒子) / 解像度: 3.5 Å 13208 7p5y EMDB-13208, PDB-7p5y: Structure of homomeric LRRC8A Volume-Regulated Anion Channel in complex with synthetic nanobody Sb3 手法: EM (単粒子) / 解像度: 3.29 Å EMDB-13212: Cryo-EM structure of homomeric LRRC8A Volume-Regulated Anion Channel in complex with synthetic nanobody Sb4 at 1:1 ratio 手法: EM (単粒子) / 解像度: 7.67 Å 13213 7p60 EMDB-13213, PDB-7p60: Structure of homomeric LRRC8A Volume-Regulated Anion Channel in complex with synthetic nanobody Sb4 at 1:0.5 ratio 手法: EM (単粒子) / 解像度: 3.8 Å 13230 7p6k EMDB-13230: Cryo-EM structure of homomeric LRRC8A Volume-Regulated Anion Channel in complex with synthetic nanobody Sb5 PDB-7p6k: Structure of homomeric LRRC8A Volume-Regulated Anion Channel in complex with synthetic nanobody Sb5 手法: EM (単粒子) / 解像度: 3.8 Å
由来	mus musculus (ハツカネズミ) Synthetic construct (人工物)
キーワード	MEMBRANE PROTEIN / LRRC8 family / Volume-Regulated Anion Channel / leucine-rich repeat / sybody / cryo-EM