+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6edj | ||||||
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タイトル | Cryo-EM structure of Woodchuck hepatitis virus capsid | ||||||
要素 | External core antigen | ||||||
キーワード | VIRUS LIKE PARTICLE / WHV / Capsid structure | ||||||
機能・相同性 | 機能・相同性情報 virus-mediated perturbation of host defense response => GO:0019049 / microtubule-dependent intracellular transport of viral material towards nucleus / T=4 icosahedral viral capsid / : / viral penetration into host nucleus / host cell cytoplasm / symbiont entry into host cell / virus-mediated perturbation of host defense response / host cell nucleus / structural molecule activity ...virus-mediated perturbation of host defense response => GO:0019049 / microtubule-dependent intracellular transport of viral material towards nucleus / T=4 icosahedral viral capsid / : / viral penetration into host nucleus / host cell cytoplasm / symbiont entry into host cell / virus-mediated perturbation of host defense response / host cell nucleus / structural molecule activity / DNA binding / RNA binding / extracellular region 類似検索 - 分子機能 | ||||||
生物種 | Woodchuck hepatitis virus (マーモセット肝炎ウイルス) | ||||||
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: 4.52 Å | ||||||
データ登録者 | Zhao, Z. / Wang, J.C. / Zlotnick, A. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: J Virol / 年: 2019 タイトル: Structural Differences between the Woodchuck Hepatitis Virus Core Protein in the Dimer and Capsid States Are Consistent with Entropic and Conformational Regulation of Assembly. 著者: Zhongchao Zhao / Joseph Che-Yen Wang / Giovanni Gonzalez-Gutierrez / Balasubramanian Venkatakrishnan / Roi Asor / Daniel Khaykelson / Uri Raviv / Adam Zlotnick / 要旨: Hepadnaviruses are hepatotropic enveloped DNA viruses with an icosahedral capsid. Hepatitis B virus (HBV) causes chronic infection in an estimated 240 million people; woodchuck hepatitis virus (WHV), ...Hepadnaviruses are hepatotropic enveloped DNA viruses with an icosahedral capsid. Hepatitis B virus (HBV) causes chronic infection in an estimated 240 million people; woodchuck hepatitis virus (WHV), an HBV homologue, has been an important model system for drug development. The dimeric capsid protein (Cp) has multiple functions during the viral life cycle and thus has become an important target for a new generation of antivirals. Purified HBV and WHV Cp spontaneously assemble into 120-dimer capsids. Though they have 65% identity, WHV Cp has error-prone assembly with stronger protein-protein association. We have taken advantage of the differences in assemblies to investigate the basis of assembly regulation. We determined the structures of the WHV capsid to 4.5-Å resolution by cryo-electron microscopy (cryo-EM) and of the WHV Cp dimer to 2.9-Å resolution by crystallography and examined the biophysical properties of the dimer. We found, in dimer, that the subdomain that makes protein-protein interactions is partially disordered and rotated 21° from its position in capsid. This subdomain is susceptible to proteolysis, consistent with local disorder. WHV assembly shows similar susceptibility to HBV antiviral molecules, suggesting that HBV assembly follows similar transitions. These data show that there is an entropic cost for assembly that is compensated for by the energetic gain of burying hydrophobic interprotein contacts. We propose a series of stages in assembly that incorporate a disorder-to-order transition and structural shifts. We suggest that a cascade of structural changes may be a common mechanism for regulating high-fidelity capsid assembly in HBV and other viruses. Virus capsids assemble spontaneously with surprisingly high fidelity. This requires strict geometry and a narrow range of association energies for these protein-protein interactions. It was hypothesized that requiring subunits to undergo a conformational change to become assembly active could regulate assembly by creating an energetic barrier and attenuating association. We found that woodchuck hepatitis virus capsid protein undergoes structural transitions between its dimeric and its 120-dimer capsid states. It is likely that the closely related hepatitis B virus capsid protein undergoes similar structural changes, which has implications for drug design. Regulation of assembly by structural transition may be a common mechanism for many viruses. | ||||||
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 | 6edj.cif.gz | 110.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6edj.ent.gz | 88.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6edj.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 | 6edj_validation.pdf.gz | 939 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6edj_full_validation.pdf.gz | 941.7 KB | 表示 | |
XML形式データ | 6edj_validation.xml.gz | 27.3 KB | 表示 | |
CIF形式データ | 6edj_validation.cif.gz | 39.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ed/6edj ftp://data.pdbj.org/pub/pdb/validation_reports/ed/6edj | 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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対称性 | 点対称性: (シェーンフリース記号: I (正20面体型対称)) |
-要素
#1: タンパク質 | 分子量: 17126.465 Da / 分子数: 4 / 断片: UNP residues 31-179 / 由来タイプ: 組換発現 由来: (組換発現) Woodchuck hepatitis virus (マーモセット肝炎ウイルス) 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P0C6J4, UniProt: P0C6J2*PLUS |
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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: Woodchuck hepatitis virus / タイプ: VIRUS / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Woodchuck hepatitis virus (マーモセット肝炎ウイルス) |
由来(組換発現) | 生物種: Escherichia coli (大腸菌) |
ウイルスについての詳細 | 中空か: YES / エンベロープを持つか: NO / 単離: OTHER / タイプ: VIRUS-LIKE PARTICLE |
緩衝液 | pH: 7.5 |
試料 | 濃度: 10 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: unspecified |
急速凍結 | 凍結剤: ETHANE / 湿度: 100 % |
-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: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 30 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
対称性 | 点対称性: I (正20面体型対称) | ||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 4.52 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 7911 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL | ||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 6ECS Accession code: 6ECS / Source name: PDB / タイプ: experimental model |