4QXX
Structure of the amyloid forming peptide GNLVS (residues 26-30) from the eosinophil major basic protein (EMBP)
Summary for 4QXX
| Entry DOI | 10.2210/pdb4qxx/pdb |
| Descriptor | Bone marrow proteoglycan (2 entities in total) |
| Functional Keywords | amyloid-like protofibril, protein fibril |
| Biological source | Homo sapiens (human) |
| Cellular location | Bone marrow proteoglycan: Secreted. Eosinophil granule major basic protein: Cytoplasmic vesicle, secretory vesicle: P13727 |
| Total number of polymer chains | 1 |
| Total formula weight | 488.54 |
| Authors | Soriaga, A.B.,Soragni, A.,Sawaya, M.R.,Eisenberg, D. (deposition date: 2014-07-22, release date: 2015-03-18, Last modification date: 2024-02-28) |
| Primary citation | 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 Cited by 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: 25728769DOI: 10.1016/j.molcel.2015.01.026 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.445 Å) |
Structure validation
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