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基本情報
登録情報 | データベース: PDB / ID: 8a7o | ||||||||||||
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タイトル | beta-2-microglobulin DeltaN6 amyloid fibril form 2PFa | ||||||||||||
![]() | Beta-2-microglobulin form pI 5.3 | ||||||||||||
![]() | PROTEIN FIBRIL / Amyloid / fibril / helical / cross-beta / dialysis-related amyloidosis | ||||||||||||
機能・相同性 | ![]() positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC ...positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / cellular response to iron(III) ion / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / negative regulation of forebrain neuron differentiation / regulation of erythrocyte differentiation / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / regulation of iron ion transport / response to molecule of bacterial origin / MHC class I peptide loading complex / HFE-transferrin receptor complex / T cell mediated cytotoxicity / 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 / negative regulation of neurogenesis / peptide antigen assembly with MHC class II protein complex / positive regulation of receptor-mediated endocytosis / MHC class II protein complex / cellular response to nicotine / positive regulation of T cell mediated cytotoxicity / specific granule lumen / recycling endosome membrane / phagocytic vesicle membrane / positive regulation of cellular senescence / peptide antigen binding / negative regulation of epithelial cell proliferation / 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 / Modulation by Mtb of host immune system / sensory perception of smell / positive regulation of T cell activation / positive regulation of protein binding / tertiary granule lumen / DAP12 signaling / negative regulation of neuron projection development / MHC class II protein complex binding / late endosome membrane / iron ion transport / ER-Phagosome pathway / early endosome membrane / T cell differentiation in thymus / protein refolding / protein homotetramerization / intracellular iron ion homeostasis / amyloid fibril formation / learning or memory / Amyloid fiber formation / endoplasmic reticulum lumen / Golgi membrane / lysosomal membrane / external side of plasma membrane / focal adhesion / Neutrophil degranulation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / structural molecule activity / Golgi apparatus / endoplasmic reticulum / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytosol 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() | ||||||||||||
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 Å | ||||||||||||
![]() | Wilkinson, M. / Gallardo, R. / Radford, S.E. / Ranson, N.A. | ||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Disease-relevant β-microglobulin variants share a common amyloid fold. 著者: Martin Wilkinson / Rodrigo U Gallardo / Roberto Maya Martinez / Nicolas Guthertz / Masatomo So / Liam D Aubrey / Sheena E Radford / Neil A Ranson / ![]() ![]() ![]() 要旨: β-microglobulin (βm) and its truncated variant ΔΝ6 are co-deposited in amyloid fibrils in the joints, causing the disorder dialysis-related amyloidosis (DRA). Point mutations of βm result in ...β-microglobulin (βm) and its truncated variant ΔΝ6 are co-deposited in amyloid fibrils in the joints, causing the disorder dialysis-related amyloidosis (DRA). Point mutations of βm result in diseases with distinct pathologies. βm-D76N causes a rare systemic amyloidosis with protein deposited in the viscera in the absence of renal failure, whilst βm-V27M is associated with renal failure, with amyloid deposits forming predominantly in the tongue. Here we use cryoEM to determine the structures of fibrils formed from these variants under identical conditions in vitro. We show that each fibril sample is polymorphic, with diversity arising from a 'lego-like' assembly of a common amyloid building block. These results suggest a 'many sequences, one amyloid fold' paradigm in contrast with the recently reported 'one sequence, many amyloid folds' behaviour of intrinsically disordered proteins such as tau and Aβ. | ||||||||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロード
PDBx/mmCIF形式 | ![]() | 100.4 KB | 表示 | ![]() |
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PDB形式 | ![]() | 81 KB | 表示 | ![]() |
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その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 32.4 KB | 表示 | |
CIF形式データ | ![]() | 43.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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
#1: タンパク質 | 分子量: 11153.478 Da / 分子数: 6 / 変異: deltaN6, K6M / 由来タイプ: 組換発現 詳細: Naturally occuring deltaN6 variant with methionine added prior to peptide sequence to initiate bacterial expression. 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: FILAMENT / 3次元再構成法: らせん対称体再構成法 |
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試料調製
構成要素 | 名称: Amyloid fibril polymorph 2PFa of the beta-2-microglobulin deltaN6 variant. タイプ: COMPLEX 詳細: Recombinantly expressed and fibrillated in vitro at pH 6.2 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: 6.2 | |||||||||||||||
緩衝液成分 |
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試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: Fibrillation conditions: 20 uM monomeric b2m-DN6 at 37C with shaking at 600 rpm for 2-3 weeks | |||||||||||||||
試料支持 | 詳細: The grid was plasma cleaned prior to double addition of Graphene oxide-DDM mixture then used immediately for sample application and vitrification グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: EMS Lacey Carbon | |||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 90 % / 凍結前の試料温度: 277 K / 詳細: 6s blot |
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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 / 倍率(公称値): 96000 X / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1300 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm / アライメント法: COMA FREE |
試料ホルダ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 7 sec. / 電子線照射量: 43 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 撮影したグリッド数: 1 / 実像数: 4095 詳細: 1687 raw EER frames were collected per image and combined into 40 fractions for processing |
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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: -0.82 ° / 軸方向距離/サブユニット: 4.85 Å / らせん対称軸の対称性: C1 | ||||||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 612949 詳細: Manually picked a subset of images to train a model for automatic fibril segment picking in crYOLO | ||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 133576 / 対称性のタイプ: HELICAL | ||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | B value: 53 / プロトコル: AB INITIO MODEL / 空間: REAL |