8OQI
Cryo-EM structure of the wild-type alpha-synuclein fibril.
Summary for 8OQI
| Entry DOI | 10.2210/pdb8oqi/pdb |
| EMDB information | 17111 |
| Descriptor | Alpha-synuclein (1 entity in total) |
| Functional Keywords | alpha-synuclein, amyloid, fibril, parkinson's disease, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 10 |
| Total formula weight | 144761.08 |
| Authors | Pesch, V.,Reithofer, S.,Ma, L.,Flores-Fernandez, J.M.,Oezduezenciler, P.,Busch, Y.,Lien, Y.,Rudtke, O.,Frieg, B.,Schroeder, G.F.,Wille, H.,Tamgueney, G. (deposition date: 2023-04-12, release date: 2024-03-13, Last modification date: 2024-05-15) |
| Primary citation | Pesch, V.,Flores-Fernandez, J.M.,Reithofer, S.,Ma, L.,Ozduzenciler, P.,Busch, Y.,Sriraman, A.,Wang, Y.,Amidian, S.,Kroepel, C.V.M.,Muller, L.,Lien, Y.,Rudtke, O.,Frieg, B.,Schroder, G.F.,Wille, H.,Tamguney, G. Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson's disease. Brain, 147:1644-1652, 2024 Cited by PubMed Abstract: The pathological misfolding and aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson's disease, a progressive age-related neurodegenerative disease for which there is no cure. HET-s is a soluble fungal protein that can form assembled amyloid fibrils in its prion state. We engineered HET-s(218-298) to form four different fibrillar vaccine candidates, each displaying a specific conformational epitope present on the surface of α-synuclein fibrils. Vaccination with these four vaccine candidates prolonged the survival of immunized TgM83+/- mice challenged with α-synuclein fibrils by 8% when injected into the brain to model brain-first Parkinson's disease or by 21% and 22% when injected into the peritoneum or gut wall, respectively, to model body-first Parkinson's disease. Antibodies from fully immunized mice recognized α-synuclein fibrils and brain homogenates from patients with Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Conformation-specific vaccines that mimic epitopes present only on the surface of pathological fibrils but not on soluble monomers, hold great promise for protection against Parkinson's disease, related synucleinopathies and other amyloidogenic protein misfolding disorders. PubMed: 38428032DOI: 10.1093/brain/awae061 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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