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Molecular insights into α‐synuclein interaction with individual human core histones, linker histone, and dsDNA
Author(s) -
Jos Sneha,
Gogoi Hemanga,
Prasad Thazhe Kootteri,
Hurakadli Manjunath A.,
Kamariah Neelagandan,
Padmanabhan Balasundaram,
Padavattan Sivaraman
Publication year - 2021
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.4167
Subject(s) - linker , histone , chemistry , linker dna , biophysics , core (optical fiber) , computational biology , biochemistry , microbiology and biotechnology , histone h1 , biology , dna , physics , computer science , operating system , optics
α‐Synuclein (αS) plays a key role in Parkinson's disease (PD). The αS nuclear role, its binding affinity and specificity to histones and dsDNA remains unknown. Here, we have measured the binding affinity ( K d ) between αS wild‐type (wt) and PD‐specific αS S129‐phosphorylation mimicking (S129E) mutant with full‐length and flexible tail truncated individual core histones (H2a, H2b, H3, and H4), linker histone (H1), and carried out αS‐dsDNA interaction studies. This study revealed that αS(wt) interacts specifically with N‐terminal flexible tails of histone H3, H4, and flexible tails of H1. The αS(S129E) mutant recognizes histones similar to αS(wt) but binds with higher affinity. Intriguingly, αS(S129E) showed a binding affinity for control proteins (bovine serum albumin and lysozyme), while no interaction was seen for αS(wt). Based on our above observation, we contemplate that the physio‐chemical properties of αS with S129‐phosphorylation has changed compared to αS(wt), resulting in interaction for other proteins, which is the basis for Lewy body formation. Besides, this study showed αS binding to dsDNA is weak and nonspecific. Overall, αS specificity for histone binding suggests that its nuclear role is possibly driven through histone interaction.