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	Engineered disulfide reveals structural dynamics of locked SARS-CoV-2 spike.
ジャーナル・号・ページ	PLoS Pathog, Vol. 18, Issue 7, Page e1010583, Year 2022
掲載日	2022年7月29日
著者	Kun Qu / Qiuluan Chen / Katarzyna A Ciazynska / Banghui Liu / Xixi Zhang / Jingjing Wang / Yujie He / Jiali Guan / Jun He / Tian Liu / Xiaofei Zhang / Andrew P Carter / Xiaoli Xiong / John A G Briggs /
PubMed 要旨	The spike (S) protein of SARS-CoV-2 has been observed in three distinct pre-fusion conformations: locked, closed and open. Of these, the function of the locked conformation remains poorly understood. ...The spike (S) protein of SARS-CoV-2 has been observed in three distinct pre-fusion conformations: locked, closed and open. Of these, the function of the locked conformation remains poorly understood. Here we engineered a SARS-CoV-2 S protein construct "S-R/x3" to arrest SARS-CoV-2 spikes in the locked conformation by a disulfide bond. Using this construct we determined high-resolution structures confirming that the x3 disulfide bond has the ability to stabilize the otherwise transient locked conformations. Structural analyses reveal that wild-type SARS-CoV-2 spike can adopt two distinct locked-1 and locked-2 conformations. For the D614G spike, based on which all variants of concern were evolved, only the locked-2 conformation was observed. Analysis of the structures suggests that rigidified domain D in the locked conformations interacts with the hinge to domain C and thereby restrains RBD movement. Structural change in domain D correlates with spike conformational change. We propose that the locked-1 and locked-2 conformations of S are present in the acidic high-lipid cellular compartments during virus assembly and egress. In this model, release of the virion into the neutral pH extracellular space would favour transition to the closed or open conformations. The dynamics of this transition can be altered by mutations that modulate domain D structure, as is the case for the D614G mutation, leading to changes in viral fitness. The S-R/x3 construct provides a tool for the further structural and functional characterization of the locked conformations of S, as well as how sequence changes might alter S assembly and regulation of receptor binding domain dynamics.
リンク	PLoS Pathog / PubMed:35905112 / PubMed Central
手法	EM (単粒子)
解像度	2.6 - 3.5 Å
構造データ	33453 7xtz EMDB-33453, PDB-7xtz: Structure of SARS-CoV-2 Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site), Locked-1 Conformation 手法: EM (単粒子) / 解像度: 2.8 Å 33454 7xu0 EMDB-33454, PDB-7xu0: Structure of SARS-CoV-2 Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site), Locked-211 Conformation 手法: EM (単粒子) / 解像度: 2.9 Å 33455 7xu1 EMDB-33455, PDB-7xu1: Structure of SARS-CoV-2 Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site), Locked-122 Conformation 手法: EM (単粒子) / 解像度: 3.0 Å 33456 7xu2 EMDB-33456, PDB-7xu2: Structure of SARS-CoV-2 Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site), Locked-2 Conformation 手法: EM (単粒子) / 解像度: 3.2 Å 33457 7xu3 EMDB-33457, PDB-7xu3: Structure of SARS-CoV-2 Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site), Closed Conformation 手法: EM (単粒子) / 解像度: 3.0 Å 33458 7xu4 EMDB-33458, PDB-7xu4: Structure of SARS-CoV-2 D614G Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site), Locked-2 Conformation 手法: EM (単粒子) / 解像度: 3.2 Å 33459 7xu5 EMDB-33459, PDB-7xu5: Structure of SARS-CoV-2 D614G Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site), Closed Conformation 手法: EM (単粒子) / 解像度: 3.1 Å 33460 7xu6 EMDB-33460, PDB-7xu6: Structure of SARS-CoV-2 Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site), incubated in Low pH after 40-Day Storage in PBS, Locked-2 Conformation 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-33461: Structure of SARS-CoV-2 Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site) after 40-Day Storage in PBS, Closed Conformation 手法: EM (単粒子) / 解像度: 2.6 Å EMDB-33462: Structure of SARS-CoV-2 Spike Protein with Engineered x3 Disulfide (x3(D427C, V987C) and single Arg S1/S2 cleavage site), incubated in Low pH after 40-Day Storage in PBS, Closed Conformation 手法: EM (単粒子) / 解像度: 3.5 Å EMDB-33463: Structure of SARS-CoV-2 D614G spike protein (single Arg S1/S2 cleavage site), Closed Conformation 手法: EM (単粒子) / 解像度: 3.0 Å EMDB-33464: Structure of SARS-Cov-2 D614G spike protein (single Arg S1/S2 cleavage site), Open Conformation 手法: EM (単粒子) / 解像度: 3.1 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-BLA: BILIVERDINE IX ALPHA / 19,24-ジヒドロ-1-ヒドロキシ-3,7,13,18-テトラメチル-2,17-ジビニル-19-オキソ-22H-ビリ(以下略) ChemComp-EIC: LINOLEIC ACID / リノ-ル酸 / リノール酸
由来	severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2)
キーワード	VIRAL PROTEIN (ウイルスタンパク質) / protein engineering (タンパク質工学) / spike protein (スパイクタンパク質) / SARS-CoV-2 (SARSコロナウイルス2)