4QXX

Structure of the amyloid forming peptide GNLVS (residues 26-30) from the eosinophil major basic protein (EMBP)

4QXX の概要

• エントリーDOI: 10.2210/pdb4qxx/pdb
• 分子名称: Bone marrow proteoglycan (2 entities in total)
• 機能のキーワード: amyloid-like protofibril, protein fibril
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Bone marrow proteoglycan: Secreted. Eosinophil granule major basic protein: Cytoplasmic vesicle, secretory vesicle: P13727
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 488.54

構造登録者

Soriaga, A.B.,Soragni, A.,Sawaya, M.R.,Eisenberg, D. (登録日: 2014-07-22, 公開日: 2015-03-18, 最終更新日: 2024-02-28)

主引用文献

Soragni, A.,Yousefi, S.,Stoeckle, C.,Soriaga, A.B.,Sawaya, M.R.,Kozlowski, E.,Schmid, I.,Radonjic-Hoesli, S.,Boutet, S.,Williams, G.J.,Messerschmidt, M.,Seibert, M.M.,Cascio, D.,Zatsepin, N.A.,Burghammer, M.,Riekel, C.,Colletier, J.P.,Riek, R.,Eisenberg, D.S.,Simon, H.U.
Toxicity of Eosinophil MBP Is Repressed by Intracellular Crystallization and Promoted by Extracellular Aggregation.
Mol.Cell, 57:1011-1021, 2015

PubMed Abstract: Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly.

PubMed: 25728769
DOI: 10.1016/j.molcel.2015.01.026

実験手法

X-RAY DIFFRACTION (1.445 Å)