+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7k1s | |||||||||||||||||||||
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タイトル | The N-terminus of varicella-zoster virus glycoprotein B has a functional role in fusion. | |||||||||||||||||||||
要素 | Envelope glycoprotein B | |||||||||||||||||||||
キーワード | VIRAL PROTEIN / Herpesvirus / Varicella-Zoster Virus / Pathogenesis / Fusion / Glycoprotein B | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 host cell Golgi membrane / host cell endosome membrane / membrane => GO:0016020 / symbiont entry into host cell / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | Human herpesvirus 3 (水痘・帯状疱疹ウイルス) | |||||||||||||||||||||
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: 3.9 Å | |||||||||||||||||||||
データ登録者 | Oliver, S.L. | |||||||||||||||||||||
資金援助 | 米国, 6件
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引用 | ジャーナル: PLoS Pathog / 年: 2021 タイトル: The N-terminus of varicella-zoster virus glycoprotein B has a functional role in fusion. 著者: Stefan L Oliver / Yi Xing / Dong-Hua Chen / Soung Hun Roh / Grigore D Pintilie / David A Bushnell / Marvin H Sommer / Edward Yang / Andrea Carfi / Wah Chiu / Ann M Arvin / 要旨: Varicella-zoster virus (VZV) is a medically important alphaherpesvirus that induces fusion of the virion envelope and the cell membrane during entry, and between cells to form polykaryocytes within ...Varicella-zoster virus (VZV) is a medically important alphaherpesvirus that induces fusion of the virion envelope and the cell membrane during entry, and between cells to form polykaryocytes within infected tissues during pathogenesis. All members of the Herpesviridae, including VZV, have a conserved core fusion complex composed of glycoproteins, gB, gH and gL. The ectodomain of the primary fusogen, gB, has five domains, DI-V, of which DI contains the fusion loops needed for fusion function. We recently demonstrated that DIV is critical for fusion initiation, which was revealed by a 2.8Å structure of a VZV neutralizing mAb, 93k, bound to gB and mutagenesis of the gB-93k interface. To further assess the mechanism of mAb 93k neutralization, the binding site of a non-neutralizing mAb to gB, SG2, was compared to mAb 93k using single particle cryogenic electron microscopy (cryo-EM). The gB-SG2 interface partially overlapped with that of gB-93k but, unlike mAb 93k, mAb SG2 did not interact with the gB N-terminus, suggesting a potential role for the gB N-terminus in membrane fusion. The gB ectodomain structure in the absence of antibody was defined at near atomic resolution by single particle cryo-EM (3.9Å) of native, full-length gB purified from infected cells and by X-ray crystallography (2.4Å) of the transiently expressed ectodomain. Both structures revealed that the VZV gB N-terminus (aa72-114) was flexible based on the absence of visible structures in the cryo-EM or X-ray crystallography data but the presence of gB N-terminal peptides were confirmed by mass spectrometry. Notably, N-terminal residues 109KSQD112 were predicted to form a small α-helix and alanine substitution of these residues abolished cell-cell fusion in a virus-free assay. Importantly, transferring the 109AAAA112 mutation into the VZV genome significantly impaired viral propagation. These data establish a functional role for the gB N-terminus in membrane fusion broadly relevant to the Herpesviridae. | |||||||||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7k1s.cif.gz | 329.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7k1s.ent.gz | 265.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7k1s.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 | 7k1s_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7k1s_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 7k1s_validation.xml.gz | 120.3 KB | 表示 | |
CIF形式データ | 7k1s_validation.cif.gz | 219.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/k1/7k1s ftp://data.pdbj.org/pub/pdb/validation_reports/k1/7k1s | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 105473.250 Da / 分子数: 3 / 由来タイプ: 天然 由来: (天然) Human herpesvirus 3 (水痘・帯状疱疹ウイルス) 参照: UniProt: A0A076N502 #2: 多糖 | #3: 糖 | 研究の焦点であるリガンドがあるか | N | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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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 | 名称: Varicella-zoster virus glycoprotein B trimer. / タイプ: COMPLEX 詳細: The varicella-zoster virus glycoprotein B trimer was purified from infected MeWo cells. Entity ID: #1 / 由来: NATURAL |
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由来(天然) | 生物種: Human alphaherpesvirus 3 (水痘・帯状疱疹ウイルス) |
ウイルスについての詳細 | 単離: STRAIN |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: OTHER |
電子レンズ | モード: OTHER |
撮影 | 電子線照射量: 7.5 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.15.2_3472: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 349207 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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