+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8hxb | ||||||
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タイトル | Cryo-EM structure of MPXV M2 hexamer in complex with human B7.2 | ||||||
要素 |
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キーワード | VIRAL PROTEIN / M2 / complex / immune evasion | ||||||
機能・相同性 | 機能・相同性情報 positive regulation of lymphotoxin A production / positive regulation of T-helper 2 cell differentiation / CD40 signaling pathway / activation of protein kinase C activity / : / CD28 co-stimulation / CD28 dependent Vav1 pathway / positive regulation of immunoglobulin production / CTLA4 inhibitory signaling / positive regulation of interleukin-4 production ...positive regulation of lymphotoxin A production / positive regulation of T-helper 2 cell differentiation / CD40 signaling pathway / activation of protein kinase C activity / : / CD28 co-stimulation / CD28 dependent Vav1 pathway / positive regulation of immunoglobulin production / CTLA4 inhibitory signaling / positive regulation of interleukin-4 production / B cell activation / Interleukin-10 signaling / CD28 dependent PI3K/Akt signaling / centriolar satellite / coreceptor activity / positive regulation of T cell proliferation / T cell costimulation / positive regulation of interleukin-2 production / T cell activation / positive regulation of non-canonical NF-kappaB signal transduction / Constitutive Signaling by Aberrant PI3K in Cancer / PIP3 activates AKT signaling / signaling receptor activity / virus receptor activity / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cellular response to lipopolysaccharide / adaptive immune response / cell surface receptor signaling pathway / receptor ligand activity / immune response / external side of plasma membrane / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / cell surface / extracellular exosome / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Monkeypox virus (サル痘ウイルス) Homo sapiens (ヒト) | ||||||
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: 2.7 Å | ||||||
データ登録者 | Wang, Y. / Yang, S. / Zhao, H. / Deng, Z. | ||||||
資金援助 | 1件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Structural and functional insights into the modulation of T cell costimulation by monkeypox virus protein M2. 著者: Shangyu Yang / Yong Wang / Feiyang Yu / Rao Cheng / Yiwei Zhang / Dan Zhou / Xuanxiu Ren / Zengqin Deng / Haiyan Zhao / 要旨: The rapid spread of monkeypox in multiple countries has resulted in a global public health threat and has caused international concerns since May 2022. Poxvirus encoded M2 protein is a member of the ...The rapid spread of monkeypox in multiple countries has resulted in a global public health threat and has caused international concerns since May 2022. Poxvirus encoded M2 protein is a member of the poxvirus immune evasion family and plays roles in host immunomodulation via the regulation of innate immune response mediated by the NF-κB pathway and adaptive immune response mediated by B7 ligands. However, the interaction of monkeypox virus (MPXV) M2 with B7 ligands and structural insight into poxviral M2 function have remained elusive. Here we reveal that MPXV M2, co-existing as a hexamer and a heptamer, recognizes human B7.1 and B7.2 (hB7.1/2) with high avidities. The binding of oligomeric MPXV M2 interrupts the interactions of hB7.1/2 with CD28 and CTLA4 and subverts T cell activation mediated by B7.1/2 costimulatory signals. Cryo-EM structures of M2 in complex with hB7.1/2 show that M2 binds to the shallow concave face of hB7.1/2 and displays sterically competition with CD28 and CTLA4 for the binding to hB7.1/2. Our findings provide structural mechanisms of poxviral M2 function and immune evasion deployed by poxviruses. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8hxb.cif.gz | 373 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8hxb.ent.gz | 303.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8hxb.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 | 8hxb_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8hxb_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 8hxb_validation.xml.gz | 54 KB | 表示 | |
CIF形式データ | 8hxb_validation.cif.gz | 77.5 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/hx/8hxb ftp://data.pdbj.org/pub/pdb/validation_reports/hx/8hxb | HTTPS FTP |
-関連構造データ
関連構造データ | 35075MC 8hxaC 8hxcC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 23285.348 Da / 分子数: 6 / 由来タイプ: 組換発現 由来: (組換発現) Monkeypox virus (サル痘ウイルス) 遺伝子: O2L / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q3I8Y9 #2: タンパク質 | 分子量: 24420.646 Da / 分子数: 6 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CD86, CD28LG2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P42081 |
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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: M2-hB7.2 / タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
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 |
-電子顕微鏡撮影
顕微鏡 | モデル: JEOL CRYO ARM 300 |
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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 / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 40 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 198500 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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