+
データを開く
-
基本情報
| 登録情報 | データベース: PDB / ID: 9h28 | ||||||
|---|---|---|---|---|---|---|---|
| タイトル | Alternative conformation LGTV with TBEV prME | ||||||
要素 |
| ||||||
キーワード | VIRUS / Chimeric virus / Flavivirus / Tick-borne Encephalitis virus / Langat virus / recombinant virus | ||||||
| 機能・相同性 | 機能・相同性情報symbiont-mediated suppression of host JAK-STAT cascade via inhibition of JAK1 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / ribonucleoside triphosphate phosphatase activity / symbiont-mediated activation of host apoptosis / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of JAK1 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / ribonucleoside triphosphate phosphatase activity / symbiont-mediated activation of host apoptosis / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / clathrin-dependent endocytosis of virus by host cell / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / methyltransferase cap1 activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / protein dimerization activity / host cell perinuclear region of cytoplasm / symbiont-mediated suppression of host innate immune response / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / serine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / fusion of virus membrane with host endosome membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / host cell nucleus / virion membrane / structural molecule activity / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / metal ion binding / membrane 類似検索 - 分子機能 | ||||||
| 生物種 | tick-borne encephalitis virus-European subtype (ウイルス) Langat virus (ウイルス) | ||||||
| 手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.22 Å | ||||||
データ登録者 | Bisikalo, K. / Rosendal, E. | ||||||
| 資金援助 | スウェーデン, 1件
| ||||||
引用 | ジャーナル: J Virol / 年: 2025タイトル: Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus. 著者: Ebba Rosendal / Kyrylo Bisikalo / Stefanie M A Willekens / Marie Lindgren / Jiří Holoubek / Pavel Svoboda / Amanda Lappalainen / Ebba Könighofer / Ekaterina Mirgorodskaya / Rickard Nordén ...著者: Ebba Rosendal / Kyrylo Bisikalo / Stefanie M A Willekens / Marie Lindgren / Jiří Holoubek / Pavel Svoboda / Amanda Lappalainen / Ebba Könighofer / Ekaterina Mirgorodskaya / Rickard Nordén / Federico Morini / William Rosenbaum / Daniel Růžek / Ulf Ahlgren / Maria Anastasina / Andres Merits / Sarah J Butcher / Emma Nilsson / Anna K Överby / ![]() 要旨: Tick-borne encephalitis virus (TBEV) is a neurotropic flavivirus that causes thousands of human infections annually. Viral tropism in the brain is determined by the presence of necessary receptors, ...Tick-borne encephalitis virus (TBEV) is a neurotropic flavivirus that causes thousands of human infections annually. Viral tropism in the brain is determined by the presence of necessary receptors, entry factors, and the ability of the virus to overcome host defenses. The viral structural proteins, pre-membrane (prM), and envelope (E) play an important role in receptor binding, membrane fusion, particle maturation, and antibody neutralization. To understand how these proteins influence virus distribution and tropism in the brain, we generated a chimeric virus harboring the prM and ectodomain of E from TBEV in the background of the low-pathogenic Langat virus (LGTV). We solved the atomic structures of both the chimeric virus and LGTV to compare them to the known TBEV structure. We show that this chimeric virus remains low-pathogenic, while being structurally and antigenically similar to TBEV. Using 3D optical whole brain imaging combined with immunohistochemistry, we found that both LGTV and the chimeric virus primarily infect the cerebral cortex, with no significant differences in their localization or tropism. In contrast, TBEV shows high infection of the cerebellum and a strong preference toward Purkinje cells, indicating that factors other than the prM and E proteins are important for determining TBEV tropism in the brain. Together, this provides new insights into the roles of the structural and non-structural proteins of tick-borne flaviviruses. IMPORTANCE: Although an effective vaccine exists, there is no treatment for those infected by the tick-borne encephalitis virus (TBEV). This study aimed to better understand how the virus's surface ...IMPORTANCE: Although an effective vaccine exists, there is no treatment for those infected by the tick-borne encephalitis virus (TBEV). This study aimed to better understand how the virus's surface proteins influence viral tropism and pathogenicity. We created a chimeric virus with prM and E proteins of TBEV in the genetic background of the low-pathogenic Langat virus (LGTV). The chimeric virus remained low pathogenic, similar to LGTV. Both viruses infected similar brain regions, while TBEV showed a strong preference for the cerebellum and Purkinje cells. This means that other parts of the virus, such as non-structural proteins or NCR, likely decide how the virus behaves in the brain. This study also presents the first cryogenic electron microscopy structure of LGTV, the first whole-brain imaging of TBEV infection in mouse brain, and a new model system to study surface proteins in tick-borne flaviviruses-laying groundwork for future studies on viral tropism, antibody cross-reactivity, and virus-receptor interaction. #1: ジャーナル: Biorxiv / 年: 2024タイトル: The influence of the pre-membrane and envelope proteins on structure, pathogenicity and tropism of tick-borne encephalitis virus 著者: Rosendal, E. / Bisikalo, K. / Willekens, S.M. / Lindgren, M. / Holoubek, J. / Svoboda, P. / Lappalainen, A. / Konighofer, E. / Mirgorodskaya, E. / Norden, R. / Morini, F. / Rosenbaum, W. / ...著者: Rosendal, E. / Bisikalo, K. / Willekens, S.M. / Lindgren, M. / Holoubek, J. / Svoboda, P. / Lappalainen, A. / Konighofer, E. / Mirgorodskaya, E. / Norden, R. / Morini, F. / Rosenbaum, W. / Ruzek, D. / Ahlgren, U. / Anastasina, M. / Merits, A. / Butcher, S.J. / Nilsson, E. / Overby, A.K. | ||||||
| 履歴 |
|
-
構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
|---|
-
ダウンロードとリンク
-
ダウンロード
| PDBx/mmCIF形式 | 9h28.cif.gz | 556.1 KB | 表示 | PDBx/mmCIF形式 |
|---|---|---|---|---|
| PDB形式 | pdb9h28.ent.gz | 469.3 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 9h28.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
| その他 | その他のダウンロード |
-検証レポート
| 文書・要旨 | 9h28_validation.pdf.gz | 2.1 MB | 表示 | wwPDB検証レポート |
|---|---|---|---|---|
| 文書・詳細版 | 9h28_full_validation.pdf.gz | 2.1 MB | 表示 | |
| XML形式データ | 9h28_validation.xml.gz | 72.7 KB | 表示 | |
| CIF形式データ | 9h28_validation.cif.gz | 110 KB | 表示 | |
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/h2/9h28 ftp://data.pdbj.org/pub/pdb/validation_reports/h2/9h28 | HTTPS FTP |
-関連構造データ
-
リンク
-
集合体
| 登録構造単位 | ![]()
|
|---|---|
| 1 | ![]()
|
-
要素
| #1: タンパク質 | 分子量: 53646.422 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) tick-borne encephalitis virus-European subtype (ウイルス), (組換発現) Langat virus (strain TP21) (ウイルス)株: 93/783 / 細胞株 (発現宿主): A549 MAVS -/- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: A0A7M3UFX3, UniProt: P29837#2: タンパク質 | 分子量: 8311.854 Da / 分子数: 3 / 由来タイプ: 組換発現 由来: (組換発現) tick-borne encephalitis virus-European subtype (ウイルス)株: 93/783 / 細胞株 (発現宿主): A549 MAVS -/- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: A0A7M3UFX3#3: 多糖 | #4: 化合物 | ChemComp-CPL / 研究の焦点であるリガンドがあるか | N | Has protein modification | Y | |
|---|
-実験情報
-実験
| 実験 | 手法: 電子顕微鏡法 |
|---|---|
| EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-
試料調製
| 構成要素 |
| ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 分子量 | 実験値: NO | ||||||||||||||||||||||||||||
| 由来(天然) |
| ||||||||||||||||||||||||||||
| 由来(組換発現) |
| ||||||||||||||||||||||||||||
| ウイルスについての詳細 | 中空か: NO / エンベロープを持つか: YES / 単離: OTHER / タイプ: VIRION | ||||||||||||||||||||||||||||
| ウイルス殻 | 直径: 500 nm / 三角数 (T数): 3 | ||||||||||||||||||||||||||||
| 緩衝液 | pH: 8 詳細: VP-SFM growth medium, supplemented with rapamycin and glutamate. | ||||||||||||||||||||||||||||
| 試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||||||
| 試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||
| 急速凍結 | 装置: LEICA EM GP / 凍結剤: ETHANE / 湿度: 90 % / 凍結前の試料温度: 298 K |
-
電子顕微鏡撮影
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
|---|---|
| 顕微鏡 | モデル: TFS KRIOS |
| 電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
| 電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 130000 X / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 500 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm |
| 試料ホルダ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
| 撮影 | 平均露光時間: 4.27 sec. / 電子線照射量: 40 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: TFS FALCON 4i (4k x 4k) 撮影したグリッド数: 1 / 実像数: 32122 |
-
解析
| EMソフトウェア |
| ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
| 粒子像の選択 | 選択した粒子像数: 97855 | ||||||||||||||||||||||||||||||||||||
| 対称性 | 点対称性: I (正20面体型対称) | ||||||||||||||||||||||||||||||||||||
| 3次元再構成 | 解像度: 3.22 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 18724 / アルゴリズム: FOURIER SPACE / クラス平均像の数: 2 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
| 原子モデル構築 | Source name: AlphaFold / タイプ: in silico model |
ムービー
コントローラー
万見について




tick-borne encephalitis virus-European subtype (ウイルス)
スウェーデン, 1件
引用





PDBj




Homo sapiens (ヒト)

FIELD EMISSION GUN