1. HDAC6 ZnF UBP as the Modifier of Tau Structure and Function.
- Author
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Balmik AA, Chidambaram H, Dangi A, Marelli UK, and Chinnathambi S
- Subjects
- Catalytic Domain, Humans, In Vitro Techniques, Microscopy, Electron, Transmission, Models, Molecular, Molecular Docking Simulation, Molecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Protein Aggregates, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Protein Stability, Proteolysis, Ubiquitin chemistry, Ubiquitin metabolism, Zinc Fingers, tau Proteins ultrastructure, Histone Deacetylase 6 chemistry, Histone Deacetylase 6 metabolism, tau Proteins chemistry, tau Proteins metabolism
- Abstract
Histone deacetylase 6 is a class II histone deacetylase primarily present in the cytoplasm and involved in the regulation of various cellular functions. It consists of two catalytic deacetylase domains and a unique zinc finger ubiquitin binding protein domain, which sets it apart from other HDACs. HDAC6 is known to regulate cellular activities by modifying the function of microtubules, HSP90, and cortactin through deacetylation. Apart from the catalytic activity of HDAC6, it interacts with other proteins through either the SE14 domain or the ZnF UBP domain to modulate their functions. Here, we have studied the role of the HDAC6 ZnF UBP domain as a modifier of Tau aggregation by its direct interaction with the polyproline region/repeat region of Tau. Interaction of HDAC6 ZnF UBP with Tau was found to reduce the propensity of Tau to self-aggregate and to disaggregate preformed aggregates in a concentration-dependent manner and also bring about the conformational changes in Tau protein. The interaction of HDAC6 ZnF UBP with Tau results in its degradation, suggesting either proteolytic activity of HDAC6 ZnF UBP or its role in enhancing autoproteolysis of Tau.
- Published
- 2020
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