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基本情報
登録情報 | データベース: PDB / ID: 8do4 | ||||||
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タイトル | Prefusion-stabilized Nipah virus fusion protein, dimer of trimers | ||||||
![]() | Fusion glycoprotein F0 | ||||||
![]() | VIRAL PROTEIN / Nipah / Nipah virus / NiV / fusion / F / antibody / neutralizing / conserved epitope / neutralizing antibody / prefusion / prefusion-stabilized / vaccine / vaccine design / antigen / antigen design / dimer of trimers / oligomer | ||||||
機能・相同性 | ![]() membrane fusion involved in viral entry into host cell / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / membrane 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
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: 3.2 Å | ||||||
![]() | Byrne, P.O. / Blade, E.G. / McLellan, J.S. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Prefusion stabilization of the Hendra and Langya virus F proteins. 著者: Patrick O Byrne / Elizabeth G Blade / Brian E Fisher / David R Ambrozak / Ajit R Ramamohan / Barney S Graham / Rebecca J Loomis / Jason S McLellan / ![]() 要旨: Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the genus, NiV and HeV use an attachment (G) glycoprotein and a ...Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the genus, NiV and HeV use an attachment (G) glycoprotein and a class I fusion (F) glycoprotein to invade host cells. The F protein rearranges from a metastable prefusion form to an extended postfusion form to facilitate host cell entry. Prefusion NiV F elicits higher neutralizing antibody titers than postfusion NiV F, indicating that stabilization of prefusion F may aid vaccine development. A combination of amino acid substitutions (L104C/I114C, L172F, and S191P) is known to stabilize NiV F in its prefusion conformation, although the extent to which substitutions transfer to other henipavirus F proteins is not known. Here, we perform biophysical and structural studies to investigate the mechanism of prefusion stabilization in F proteins from three henipaviruses: NiV, HeV, and Langya virus (LayV). Three known stabilizing substitutions from NiV F transfer to HeV F and exert similar structural and functional effects. One engineered disulfide bond, located near the fusion peptide, is sufficient to stabilize the prefusion conformations of both HeV F and LayV F. Although LayV F shares low overall sequence identity with NiV F and HeV F, the region around the fusion peptide exhibits high sequence conservation across all henipaviruses. Our findings indicate that substitutions targeting this site of conformational change might be applicable to prefusion stabilization of other henipavirus F proteins and support the use of NiV as a prototypical pathogen for henipavirus vaccine antigen design.IMPORTANCEPathogenic henipaviruses such as Nipah virus (NiV) and Hendra virus (HeV) cause respiratory symptoms, with severe cases resulting in encephalitis, seizures, and coma. The work described here shows that the NiV and HeV fusion (F) proteins share common structural features with the F protein from an emerging henipavirus Langya virus (LayV). Sequence alignment alone was sufficient to predict which known prefusion-stabilizing amino acid substitutions from NiV F would stabilize the prefusion conformations of HeV F and LayV F. This work also reveals an unexpected oligomeric interface shared by prefusion HeV F and NiV F. Together, these advances lay a foundation for future antigen design targeting henipavirus F proteins. In this way, Nipah virus can serve as a prototypical pathogen for the development of protective vaccines and monoclonal antibodies to prepare for potential henipavirus outbreaks. | ||||||
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 497.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 408.9 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 1.4 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.4 MB | 表示 | |
XML形式データ | ![]() | 86.2 KB | 表示 | |
CIF形式データ | ![]() | 128.2 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 27590MC ![]() 8dngC ![]() 8dnrC C: 同じ文献を引用 ( M: このデータのモデリングに利用したマップデータ |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 60039.879 Da / 分子数: 6 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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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 |
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試料調製
構成要素 | 名称: Prefusion-stabilized Nipah virus fusion protein, dimer of trimers タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 8 |
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 |
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電子顕微鏡撮影
顕微鏡 | モデル: TFS GLACIOS |
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電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1500 nm |
撮影 | 電子線照射量: 49 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
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解析
EMソフトウェア | 名称: SerialEM / カテゴリ: 画像取得 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
対称性 | 点対称性: C2 (2回回転対称) |
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 534823 / 対称性のタイプ: POINT |