7XO2

Minor polymorph in alpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-4) Parkinson's disease patient

Summary for 7XO2

• Entry DOI: 10.2210/pdb7xo2/pdb
• EMDB information: 33334
• Descriptor: Alpha-synuclein (1 entity in total)
• Functional Keywords: amyloid fibril, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 86856.65

Authors

Fan, Y.,Sun, Y.P.,Wang, J.,Liu, C. (deposition date: 2022-04-30, release date: 2022-11-30, Last modification date: 2024-07-03)

Primary citation

Fan, Y.,Sun, Y.,Yu, W.,Tao, Y.,Xia, W.,Liu, Y.,Zhao, Q.,Tang, Y.,Sun, Y.,Liu, F.,Cao, Q.,Wu, J.,Liu, C.,Wang, J.,Li, D.
Conformational change of alpha-synuclein fibrils in cerebrospinal fluid from different clinical phases of Parkinson's disease.
Structure, 31:78-, 2023

PubMed Abstract: α-Synuclein (α-syn) has been shown to form various conformational fibrils associated with different synucleinopathies. But whether the conformation of α-syn fibrils changes during disease progression is unclear. Here, we amplified α-syn aggregates from the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) staged in preclinical PD (pre-PD), middle- to late-stage PD (mid-PD), and late-stage PD (late-PD). Our results show that α-syn fibrils derived from the late-PD patient are most potent in inducing endogenous α-syn aggregation in primary neurons, followed by the mid-PD and pre-PD fibrils. By using cryo-electron microscopy, we further determined the high-resolution structures of the CSF-amplified fibrils. The structures exhibit remarkable differences in a minor but significant population of conformational species in different staged samples. Our work demonstrates structural and pathological differences between α-syn fibrils derived from PD patients at a spectrum of clinical stages, which suggests potential conformational transition of α-syn fibrils during the progression of PD.

PubMed: 36513068
DOI: 10.1016/j.str.2022.11.013

Experimental method

ELECTRON MICROSCOPY (3 Å)