+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-9031 | |||||||||
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タイトル | Cryo-EM structure of Woodchuck hepatitis virus capsid | |||||||||
マップデータ | Woodchuck hepatitis virus capsid | |||||||||
試料 |
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キーワード | WHV / Capsid structure / VIRUS LIKE PARTICLE | |||||||||
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 | 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 JC | |||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_9031.map.gz | 14.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-9031-v30.xml emd-9031.xml | 10.4 KB 10.4 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_9031_fsc.xml | 10.7 KB | 表示 | FSCデータファイル |
画像 | emd_9031.png | 89.9 KB | ||
マスクデータ | emd_9031_msk_1.map | 103 MB | マスクマップ | |
Filedesc metadata | emd-9031.cif.gz | 5.5 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-9031 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9031 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_9031.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Woodchuck hepatitis virus capsid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.72 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
ファイル | emd_9031_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Woodchuck hepatitis virus
全体 | 名称: Woodchuck hepatitis virus (マーモセット肝炎ウイルス) |
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要素 |
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-超分子 #1: Woodchuck hepatitis virus
超分子 | 名称: Woodchuck hepatitis virus / タイプ: virus / ID: 1 / 親要素: 0 / 含まれる分子: all / NCBI-ID: 35269 / 生物種: Woodchuck hepatitis virus / ウイルスタイプ: VIRUS-LIKE PARTICLE / ウイルス・単離状態: OTHER / ウイルス・エンベロープ: No / ウイルス・中空状態: Yes |
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-分子 #1: External core antigen
分子 | 名称: External core antigen / タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO |
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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) |
分子量 | 理論値: 17.126465 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MDIDPYKEFG SSYQLLNFLP LDFFPDLNAL VDTATALYEE ELTGREHCSP HHTAIRQALV CWDELTKLIA WMSSNITSEQ VRTIIVNHV NDTWGLKVRQ SLWFHLSCLT FGQHTVQEFL VSFGVWIRTP APYRPPNAPI LSTLPEHTVI UniProtKB: External core antigen |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 10 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | 詳細: unspecified |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 30.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |