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基本情報
登録情報 | データベース: PDB / ID: 6cri | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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タイトル | Structure of the cargo bound AP-1:Arf1:tetherin-Nef stable closed trimer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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![]() | VIRAL PROTEIN / PROTEIN TRANSPORT / AP / HIV / Nef / trafficking | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
機能・相同性 | ![]() negative regulation of plasmacytoid dendritic cell cytokine production / negative regulation of intracellular transport of viral material / response to interferon-beta / basolateral protein secretion / : / AP-1 adaptor complex / endosome to melanosome transport / Lysosome Vesicle Biogenesis / mitotic cleavage furrow ingression / trans-Golgi Network Vesicle Budding ...negative regulation of plasmacytoid dendritic cell cytokine production / negative regulation of intracellular transport of viral material / response to interferon-beta / basolateral protein secretion / : / AP-1 adaptor complex / endosome to melanosome transport / Lysosome Vesicle Biogenesis / mitotic cleavage furrow ingression / trans-Golgi Network Vesicle Budding / protein trimerization / response to interferon-alpha / platelet dense granule organization / Glycosphingolipid transport / metalloendopeptidase inhibitor activity / regulation of receptor internalization / symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I / melanosome assembly / Intra-Golgi traffic / regulation of Arp2/3 complex-mediated actin nucleation / symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II / Golgi Associated Vesicle Biogenesis / symbiont-mediated suppression of host apoptosis / Synthesis of PIPs at the Golgi membrane / symbiont-mediated suppression of host autophagy / clathrin adaptor activity / positive regulation of leukocyte proliferation / MHC class II antigen presentation / CD4 receptor binding / thioesterase binding / Nef Mediated CD4 Down-regulation / dendritic spine organization / determination of left/right symmetry / long-term synaptic depression / clathrin-coated vesicle / azurophil granule membrane / COPI-dependent Golgi-to-ER retrograde traffic / clathrin binding / Lysosome Vesicle Biogenesis / negative regulation of viral genome replication / Golgi Associated Vesicle Biogenesis / cell leading edge / MHC class I protein binding / Synthesis of PIPs at the plasma membrane / B cell activation / host cell Golgi membrane / response to type II interferon / intracellular copper ion homeostasis / protein targeting / COPI-mediated anterograde transport / side of membrane / vesicle-mediated transport / clathrin-coated pit / regulation of calcium-mediated signaling / viral life cycle / Neutrophil degranulation / multivesicular body / MHC class II antigen presentation / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / cytoplasmic vesicle membrane / negative regulation of cell migration / Nef mediated downregulation of MHC class I complex cell surface expression / sarcomere / small monomeric GTPase / trans-Golgi network membrane / kidney development / regulation of actin cytoskeleton organization / intracellular protein transport / trans-Golgi network / negative regulation of cell growth / response to virus / cellular response to virus / SH3 domain binding / virion component / SARS-CoV-1 activates/modulates innate immune responses / Interferon alpha/beta signaling / synaptic vesicle / presynapse / heart development / ATPase binding / defense response to virus / positive regulation of canonical NF-kappaB signal transduction / early endosome / neuron projection / postsynaptic density / symbiont-mediated suppression of host innate immune response / apical plasma membrane / protein domain specific binding / membrane raft / Golgi membrane / signaling receptor binding / lysosomal membrane / innate immune response / focal adhesion / GTPase activity / intracellular membrane-bounded organelle / synapse / Neutrophil degranulation / protein kinase binding / GTP binding 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: 6.8 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
![]() | Morris, K.L. / Buffalo, C.Z. / Hurley, J.H. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin Downregulation. 著者: Kyle L Morris / Cosmo Z Buffalo / Christina M Stürzel / Elena Heusinger / Frank Kirchhoff / Xuefeng Ren / James H Hurley / ![]() ![]() 要旨: The HIV accessory protein Nef counteracts immune defenses by subverting coated vesicle pathways. The 3.7 Å cryo-EM structure of a closed trimer of the clathrin adaptor AP-1, the small GTPase Arf1, ...The HIV accessory protein Nef counteracts immune defenses by subverting coated vesicle pathways. The 3.7 Å cryo-EM structure of a closed trimer of the clathrin adaptor AP-1, the small GTPase Arf1, HIV-1 Nef, and the cytosolic tail of the restriction factor tetherin suggested a mechanism for inactivating tetherin by Golgi retention. The 4.3 Å structure of a mutant Nef-induced dimer of AP-1 showed how the closed trimer is regulated by the dileucine loop of Nef. HDX-MS and mutational analysis were used to show how cargo dynamics leads to alternative Arf1 trimerization, directing Nef targets to be either retained at the trans-Golgi or sorted to lysosomes. Phosphorylation of the NL4-3 M-Nef was shown to regulate AP-1 trimerization, explaining how O-Nefs lacking this phosphosite counteract tetherin but most M-Nefs do not. These observations show how the higher-order organization of a vesicular coat can be allosterically modulated to direct cargoes to distinct fates. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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PDBx/mmCIF形式 | ![]() | 1.1 MB | 表示 | ![]() |
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PDB形式 | ![]() | 953.9 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 7563MC ![]() 7453C ![]() 7454C ![]() 7455C ![]() 7456C ![]() 7457C ![]() 7458C ![]() 6cm9C ![]() 6d83C ![]() 6d84C ![]() 6dffC 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 ( |
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類似構造データ |
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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
-タンパク質 , 2種, 12分子 TNcYdZCHKULV
#1: タンパク質 | 分子量: 29964.326 Da / 分子数: 6 / 断片: Tetherin UNP residues 2-26, Nef UNP residues 1-206 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() ![]() 遺伝子: BST2, nef / 発現宿主: ![]() ![]() #3: タンパク質 | 分子量: 18936.600 Da / 分子数: 6 / Mutation: Q71L / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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-AP-1 complex subunit ... , 4種, 12分子 BIJGQRMWXSab
#2: タンパク質 | 分子量: 64458.656 Da / 分子数: 3 / Mutation: K359R, E476K / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #4: タンパク質 | 分子量: 66401.055 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() #5: タンパク質 | 分子量: 48475.535 Da / 分子数: 3 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() #6: タンパク質 | 分子量: 16998.850 Da / 分子数: 3 / Mutation: C148S / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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-非ポリマー , 2種, 12分子 


#7: 化合物 | ChemComp-GTP / #8: 化合物 | ChemComp-MG / |
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-詳細
Has protein modification | 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 |
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試料調製
構成要素 | 名称: Structure of the cargo bound AP-1:Arf1:tetherin-Nef stable closed trimer タイプ: COMPLEX / Entity ID: #1-#6 / 由来: RECOMBINANT |
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分子量 | 値: 0.70 MDa / 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 詳細: 20 mM Tris at pH 8.0, 200 mM NaCl, 5 mM MgCl2, and 0.5 mM TCEP |
試料 | 濃度: 0.07 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 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 296 K |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 62.4 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 分類: 精密化 | ||||||||||||||||||||||||
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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: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 6.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 11108 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | B value: 425 / プロトコル: FLEXIBLE FIT / 空間: REAL / Target criteria: Correlation coefficient | ||||||||||||||||||||||||
拘束条件 |
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