+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7o1q | ||||||
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タイトル | Amyloid beta oligomer displayed on the alpha hemolysin scaffold | ||||||
要素 | Alpha-hemolysin hybridized Abeta | ||||||
キーワード | TOXIN / Amyloid beta oligomer / alpha hemolysin / Alzheimer's Disease | ||||||
機能・相同性 | 機能・相同性情報 cytolysis in another organism / NMDA selective glutamate receptor signaling pathway / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands ...cytolysis in another organism / NMDA selective glutamate receptor signaling pathway / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / signaling receptor activator activity / axon midline choice point recognition / smooth endoplasmic reticulum calcium ion homeostasis / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / mating behavior / Lysosome Vesicle Biogenesis / ciliary rootlet / PTB domain binding / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / Golgi-associated vesicle / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / neuron remodeling / COPII-coated ER to Golgi transport vesicle / suckling behavior / nuclear envelope lumen / dendrite development / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / The NLRP3 inflammasome / neuromuscular process controlling balance / Advanced glycosylation endproduct receptor signaling / transition metal ion binding / regulation of presynapse assembly / negative regulation of long-term synaptic potentiation / negative regulation of neuron differentiation / regulation of multicellular organism growth / intracellular copper ion homeostasis / ECM proteoglycans / trans-Golgi network membrane / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / clathrin-coated pit / protein serine/threonine kinase binding / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / forebrain development / Notch signaling pathway / neuron projection maintenance / Mitochondrial protein degradation / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / cholesterol metabolic process / positive regulation of calcium-mediated signaling / ionotropic glutamate receptor signaling pathway / response to interleukin-1 / positive regulation of glycolytic process / axonogenesis / positive regulation of mitotic cell cycle / extracellular matrix organization / adult locomotory behavior / platelet alpha granule lumen / positive regulation of interleukin-1 beta production / learning / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / positive regulation of long-term synaptic potentiation / cognition / central nervous system development / endosome lumen / locomotory behavior / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / microglial cell activation / regulation of long-term neuronal synaptic plasticity / synapse organization / serine-type endopeptidase inhibitor activity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / recycling endosome / positive regulation of interleukin-6 production / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / positive regulation of non-canonical NF-kappaB signal transduction / endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / cellular response to amyloid-beta / positive regulation of tumor necrosis factor production / G2/M transition of mitotic cell cycle / neuron projection development / cell-cell junction / Platelet degranulation / synaptic vesicle 類似検索 - 分子機能 | ||||||
生物種 | Staphylococcus aureus (黄色ブドウ球菌) 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: 3.4 Å | ||||||
データ登録者 | Wu, J. / Blum, T.B. / Farrell, D.P. / DiMaio, F. / Abrahams, J.P. / Luo, J. | ||||||
引用 | ジャーナル: Angew Chem Int Ed Engl / 年: 2021 タイトル: Cryo-electron Microscopy Imaging of Alzheimer's Amyloid-beta 42 Oligomer Displayed on a Functionally and Structurally Relevant Scaffold. 著者: Jinming Wu / Thorsten B Blum / Daniel P Farrell / Frank DiMaio / Jan Pieter Abrahams / Jinghui Luo / 要旨: Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ oligomers permeabilize cellular membranes, presumably through ...Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ oligomers permeabilize cellular membranes, presumably through a pore formation mechanism. Owing to their structural and stoichiometric heterogeneity, the structure of these pores remains to be characterized. We studied a functional Aβ42-pore equivalent, created by fusing Aβ42 to the oligomerizing, soluble domain of the α-hemolysin (αHL) toxin. Our data reveal Aβ42-αHL oligomers to share major structural, functional, and biological properties with wild-type Aβ42-pores. Single-particle cryo-EM analysis of Aβ42-αHL oligomers (with an overall 3.3 Å resolution) reveals the Aβ42-pore region to be intrinsically flexible. The Aβ42-αHL oligomers will allow many of the features of the wild-type amyloid oligomers to be studied that cannot be otherwise, and may be a highly specific antigen for the development of immuno-base diagnostics and therapies. | ||||||
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 | 7o1q.cif.gz | 674.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7o1q.ent.gz | 558.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7o1q.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 | 7o1q_validation.pdf.gz | 776.2 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7o1q_full_validation.pdf.gz | 787.3 KB | 表示 | |
XML形式データ | 7o1q_validation.xml.gz | 57.2 KB | 表示 | |
CIF形式データ | 7o1q_validation.cif.gz | 79 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/o1/7o1q ftp://data.pdbj.org/pub/pdb/validation_reports/o1/7o1q | 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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非結晶学的対称性 (NCS) | NCSドメイン:
NCSドメイン領域: Component-ID: 1 / Ens-ID: ens_1 / Beg auth comp-ID: ALA / Beg label comp-ID: ALA / End auth comp-ID: ASN / End label comp-ID: ASN / Auth seq-ID: 1 - 293 / Label seq-ID: 1 - 293
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-要素
#1: タンパク質 | 分子量: 33459.270 Da / 分子数: 7 / 由来タイプ: 組換発現 由来: (組換発現) Staphylococcus aureus (黄色ブドウ球菌), (組換発現) Homo sapiens (ヒト) 遺伝子: hly, hla, APP, A4, AD1 発現宿主: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (大腸菌) 参照: UniProt: P09616, UniProt: P05067 |
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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: Abeta42-AHL / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (大腸菌) |
緩衝液 | pH: 8 詳細: 50 mM Tris-HCl, pH 8.0, 500 mM NaCl, 250 mM imidazole and 0.38 mM DDM |
試料 | 濃度: 4.83 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: GOLD |
急速凍結 | 凍結剤: ETHANE |
-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: 55 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 141366 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 59.28 Å2 | ||||||||||||||||||||||||||||||||||||||||||
拘束条件 |
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