In-solution structure and oligomerization of human histone deacetylase 6-an integrative approach

0568950 - BTÚ 2024 RIV GB eng J - Článek v odborném periodiku
Shukla, Shivam - Komárek, Jan - Nováková, Zora - Nedvědová, Jana - Ustinova, Kseniya - Vaňková, Pavla - Kadek, A. - Uetrecht, C. - Mertens, H. - Bařinka, Cyril
In-solution structure and oligomerization of human histone deacetylase 6-an integrative approach.
FEBS Journal. Roč. 290, č. 3 (2023), s. 821-836. ISSN 1742-464X. E-ISSN 1742-4658
Grant CEP: GA ČR(CZ) GA21-31806S
Výzkumná infrastruktura: CIISB III - 90242
Institucionální podpora: RVO:86652036
Klíčová slova: acetylation * analytical ultracentrifugation * intrinsically disordered regions * oligomerization * small-angle X-ray scattering
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.4, rok: 2022
Způsob publikování: Omezený přístup
https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.16616

Human histone deacetylase 6 (HDAC6) is a structurally unique, multidomain protein implicated in a variety of physiological processes including cytoskeletal remodelling and the maintenance of cellular homeostasis. Our current understanding of the HDAC6 structure is limited to isolated domains, and a holistic picture of the full-length protein structure, including possible domain interactions, is missing. Here, we used an integrative structural biology approach to build a solution model of HDAC6 by combining experimental data from several orthogonal biophysical techniques complemented by molecular modelling. We show that HDAC6 is best described as a mosaic of folded and intrinsically disordered domains that in-solution adopts an ensemble of conformations without any stable interactions between structured domains. Furthermore, HDAC6 forms dimers/higher oligomers in a concentration-dependent manner, and its oligomerization is mediated via the positively charged N-terminal microtubule-binding domain. Our findings provide the first insights into the structure of full-length human HDAC6 and can be used as a basis for further research into structure function and physiological studies of this unique deacetylase.
Trvalý link: https://hdl.handle.net/11104/0342353