Structural and functional insights into the nuclear role of Parkinson's disease-associated α-synuclein as a histone chaperone.

ABSTRACT: α-Synuclein (αSyn) plays a critical role in the pathogenesis of 'Synucleinopathies'. Although increased nuclear αSyn localization induces neurotoxicity, its definitive physiological role remains elusive. Previous studies on nuclear αSyn are limited to its interactions with individual histones and dsDNA, leaving a significant gap in understanding its interactions with assembled histone H2a-H2b dimer and (H3-H4)₂ tetramer, as well as its role in chromatin regulation. Here, we demonstrate that αSyn binds specifically to both H2a-H2b and (H3-H4)₂ with high affinity. Truncation studies reveal that αSyn(1-103) region interacts with (H3-H4)₂, while the acidic (121-140) C-terminal end is crucial for H2a-H2b binding and contains a conserved DEF/YxP motif present in

SUBMITTER: Jos S 

PROVIDER: S-EPMC12062221 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature