+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6gk3 | ||||||||||||||||||
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タイトル | Two protofilament beta-2-microglobulin amyloid fibril | ||||||||||||||||||
要素 | Beta-2-microglobulinΒ2-ミクログロブリン | ||||||||||||||||||
キーワード | PROTEIN FIBRIL / amyloid (アミロイド) / b2m | ||||||||||||||||||
機能・相同性 | 機能・相同性情報 positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / early endosome lumen / positive regulation of receptor binding / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent ...positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / early endosome lumen / positive regulation of receptor binding / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / cellular response to iron(III) ion / negative regulation of forebrain neuron differentiation / ER to Golgi transport vesicle membrane / response to molecule of bacterial origin / regulation of erythrocyte differentiation / regulation of iron ion transport / MHC class I peptide loading complex / HFE-transferrin receptor complex / T cell mediated cytotoxicity / cellular response to iron ion / antigen processing and presentation of endogenous peptide antigen via MHC class I / positive regulation of T cell cytokine production / MHC class I protein complex / multicellular organismal-level iron ion homeostasis / positive regulation of T cell mediated cytotoxicity / peptide antigen assembly with MHC class II protein complex / negative regulation of neurogenesis / MHC class II protein complex / positive regulation of receptor-mediated endocytosis / cellular response to nicotine / recycling endosome membrane / phagocytic vesicle membrane / specific granule lumen / peptide antigen binding / positive regulation of cellular senescence / antigen processing and presentation of exogenous peptide antigen via MHC class II / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Interferon gamma signaling / positive regulation of immune response / negative regulation of epithelial cell proliferation / Modulation by Mtb of host immune system / positive regulation of T cell activation / sensory perception of smell / negative regulation of neuron projection development / tertiary granule lumen / DAP12 signaling / MHC class II protein complex binding / late endosome membrane / T cell differentiation in thymus / positive regulation of protein binding / ER-Phagosome pathway / iron ion transport / protein refolding / early endosome membrane / protein homotetramerization / intracellular iron ion homeostasis / amyloid fibril formation / learning or memory / Amyloid fiber formation / lysosomal membrane / 小胞体 / external side of plasma membrane / ゴルジ体 / focal adhesion / Neutrophil degranulation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ゴルジ体 / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / 生体膜 / identical protein binding / 細胞膜 / 細胞質基質 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||||||||
手法 | 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.975 Å | ||||||||||||||||||
データ登録者 | Iadanza, M.G. / Ranson, N.A. | ||||||||||||||||||
資金援助 | 英国, 米国, 5件
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引用 | ジャーナル: Nat Commun / 年: 2018 タイトル: The structure of a β-microglobulin fibril suggests a molecular basis for its amyloid polymorphism. 著者: Matthew G Iadanza / Robert Silvers / Joshua Boardman / Hugh I Smith / Theodoros K Karamanos / Galia T Debelouchina / Yongchao Su / Robert G Griffin / Neil A Ranson / Sheena E Radford / 要旨: All amyloid fibrils contain a cross-β fold. How this structure differs in fibrils formed from proteins associated with different diseases remains unclear. Here, we combine cryo-EM and MAS-NMR to ...All amyloid fibrils contain a cross-β fold. How this structure differs in fibrils formed from proteins associated with different diseases remains unclear. Here, we combine cryo-EM and MAS-NMR to determine the structure of an amyloid fibril formed in vitro from β-microglobulin (βm), the culprit protein of dialysis-related amyloidosis. The fibril is composed of two identical protofilaments assembled from subunits that do not share βm's native tertiary fold, but are formed from similar β-strands. The fibrils share motifs with other amyloid fibrils, but also contain unique features including π-stacking interactions perpendicular to the fibril axis and an intramolecular disulfide that stabilises the subunit fold. We also describe a structural model for a second fibril morphology and show that it is built from the same subunit fold. The results provide insights into the mechanisms of fibril formation and the commonalities and differences within the amyloid fold in different protein sequences. | ||||||||||||||||||
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 | 6gk3.cif.gz | 98.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6gk3.ent.gz | 80.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6gk3.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/gk/6gk3 ftp://data.pdbj.org/pub/pdb/validation_reports/gk/6gk3 | HTTPS FTP |
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-関連構造データ
関連構造データ | 0014MC 0021C 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 | |
電子顕微鏡画像生データ | EMPIAR-10207 (タイトル: Beta-2-microglobulin fibrils with multiple polymorphs formed at pH 2 Data size: 294.3 Data #1: Aligned, dose-weighted micrographs [micrographs - single frame]) |
-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: 7635.446 Da / 分子数: 8 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: B2M, CDABP0092, HDCMA22P / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P61769 |
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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: FILAMENT / 3次元再構成法: らせん対称体再構成法 |
-試料調製
構成要素 | 名称: two protofilament beta-2-microglobulin amyloid fibril タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT | ||||||||||||||||||||
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分子量 | 値: 53.3 kDa/nm / 実験値: NO | ||||||||||||||||||||
由来(天然) | 生物種: Homo sapiens (ヒト) | ||||||||||||||||||||
由来(組換発現) | 生物種: Escherichia coli (大腸菌) | ||||||||||||||||||||
緩衝液 | pH: 2.5 | ||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 0.025 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: Quiescent growth at 0.25 mg/ml for 5 weeks, diluted 10x with buffer | ||||||||||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: Quantifoil R3.5/1 | ||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK II / 凍結剤: ETHANE / 湿度: 80 % / 凍結前の試料温度: 281.15 K |
-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 FIELDBright-field microscopy / 倍率(公称値): 130000 X / 最大 デフォーカス(公称値): 3.25 nm / 最小 デフォーカス(公称値): 1.75 nm / Cs: 2.7 mm / C2レンズ絞り径: 100 µm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 10 sec. / 電子線照射量: 38.5 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 撮影したグリッド数: 1 / 実像数: 5549 |
画像スキャン | 動画フレーム数/画像: 40 / 利用したフレーム数/画像: 3-40 |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
らせん対称 | 回転角度/サブユニット: -0.608 ° / 軸方向距離/サブユニット: 4.83 Å / らせん対称軸の対称性: C2 | ||||||||||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 99000 / 詳細: 300 x 300 pixel Overlapping segments 90% overlap | ||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.975 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 11035 / アルゴリズム: FOURIER SPACE / クラス平均像の数: 1 / 対称性のタイプ: HELICAL | ||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: OTHER / 空間: REAL | ||||||||||||||||||||||||||||||||||||||||||||
精密化 | 最高解像度: 3.9 Å |