- EMDB-15223: beta-2-microglobulin DeltaN6 amyloid fibril form 2PFb -
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基本情報
登録情報
データベース: EMDB / ID: EMD-15223
タイトル
beta-2-microglobulin DeltaN6 amyloid fibril form 2PFb
マップデータ
CryoEM helical symmetrised map of b2m-DN6 Form 2PFb (sharpening b-factor of -37)
試料
複合体: Amyloid fibril polymorph 2PFb of the beta-2-microglobulin deltaN6 variant.
タンパク質・ペプチド: Beta-2-microglobulin form pI 5.3
機能・相同性
機能・相同性情報
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 / negative regulation of receptor binding / DAP12 interactions / 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 / negative regulation of receptor binding / DAP12 interactions / 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 / peptide antigen assembly with MHC class I protein complex / ER to Golgi transport vesicle membrane / 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 / positive regulation of receptor-mediated endocytosis / peptide antigen assembly with MHC class II protein complex / 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 / peptide antigen binding / positive regulation of cellular senescence / 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 / positive regulation of T cell activation / sensory perception of smell / negative regulation of neuron projection development / positive regulation of protein binding / tertiary granule lumen / DAP12 signaling / MHC class II protein complex binding / early endosome membrane / late endosome membrane / iron ion transport / ER-Phagosome pathway / T cell differentiation in thymus / protein refolding / protein homotetramerization / intracellular iron ion homeostasis / amyloid fibril formation / learning or memory / Amyloid fiber formation / Golgi membrane / endoplasmic reticulum lumen / external side of plasma membrane / lysosomal 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
ジャーナル: Nat Commun / 年: 2023 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.
モデル: EMS Lacey Carbon / 材質: COPPER / メッシュ: 300 / 支持フィルム - 材質: GRAPHENE OXIDE / 支持フィルム - トポロジー: CONTINUOUS / 前処理 - タイプ: PLASMA CLEANING / 前処理 - 時間: 60 sec. 詳細: The grid was plasma cleaned prior to 2x application of graphene oxide-DDM mixture, then grid was used immediately for sample application and vitrification
凍結
凍結剤: ETHANE / チャンバー内湿度: 90 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV / 詳細: 6s blot.
詳細
Fibrillation conditions: 20 uM monomeric b2m-DN6 at 37C with shaking at 600 rpm for 2-3 weeks
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
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 / 平均露光時間: 7.0 sec. / 平均電子線量: 43.0 e/Å2 詳細: 1687 raw EER frames were collected per image and combined into 40 fractions for processing