Surabhi Mehra, Sahil Ahlawat, Harish Kumar, Debalina Datta, Ambuja Navalkar, Nitu Singh, Komal Patel, Laxmikant Gadhe, Pradeep Kadu, Rakesh Kumar, Narendra N Jha, Arunima Sakunthala, Ajay S Sawner, Ranjith Padinhateeri, Jayant B Udgaonkar, Vipin Agarwal, Samir K Maji
α-Synuclein (α-Syn) amyloids in synucleinopathies are suggested to be structurally and functionally diverse, reminiscent of prion-like strains. The mechanism of how the aggregation of the same precursor protein results in the formation of fibril polymorphs remains elusive. Here, we demonstrate the structure-function relationship of two polymorphs, pre-matured fibrils (PMFs) and helix-matured fibrils (HMFs), based on α-Syn aggregation intermediates. These polymorphs display the structural differences as demonstrated by solid-state NMR and mass spectrometry studies and also possess different cellular activities such as seeding, internalization, and cell-to-cell transfer of aggregates...
October 15, 2022: Journal of Molecular Biology