Phosphoryl group wires stabilize pathological tau fibrils as revealed by multiple quantum spin counting NMR.

ABSTRACT: Hyperphosphorylation of the protein tau is one of the biomarkers of neurodegenerative diseases in the category of tauopathies. However, the molecular level, mechanistic, role of this common post-translational modification (PTM) in enhancing or reducing the aggregation propensity of tau is unclear, especially considering that combinatorial phosphorylation of multiple sites can have complex, non-additive, effects on tau protein aggregation. Since tau proteins stack in register and parallel to elongate into pathological fibrils, phosphoryl groups from adjacent tau strands with 4.8 Å separation must find an energetically favorable spatial arrangement. At first glance, this appears to be an unfavorable configuration due to the proximity of negative charges between phosphate groups from adjacent

SUBMITTER: Potnuru LR 

PROVIDER: S-EPMC11343107 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature