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@article{2409881,
author = {Shukla, Shivam and Komarek, Jan and Novakova, Zora and Nedvedova, Jana and Ustinova, Kseniya and Vankova, Pavla and Kadek, Alan and Uetrecht, Charlotte and Mertens, Haydyn and Barinka, Cyril},
article_location = {MALDEN},
article_number = {3},
doi = {http://dx.doi.org/10.1111/febs.16616},
keywords = {acetylation; analytical ultracentrifugation; intrinsically disordered regions; oligomerization; small-angle X-ray scattering},
language = {eng},
issn = {1742-464X},
journal = {FEBS Journal},
title = {In-solution structure and oligomerization of human histone deacetylase 6-an integrative approach},
url = {https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.16616},
volume = {290},
year = {2023}
}
TY - JOUR
ID - 2409881
AU - Shukla, Shivam - Komarek, Jan - Novakova, Zora - Nedvedova, Jana - Ustinova, Kseniya - Vankova, Pavla - Kadek, Alan - Uetrecht, Charlotte - Mertens, Haydyn - Barinka, Cyril
PY - 2023
TI - In-solution structure and oligomerization of human histone deacetylase 6-an integrative approach
JF - FEBS Journal
VL - 290
IS - 3
SP - 821-836
EP - 821-836
PB - Blackwell
SN - 1742464X
KW - acetylation
KW - analytical ultracentrifugation
KW - intrinsically disordered regions
KW - oligomerization
KW - small-angle X-ray scattering
UR - https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.16616
N2 - 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.
ER -
SHUKLA, Shivam, Jan KOMAREK, Zora NOVAKOVA, Jana NEDVEDOVA, Kseniya USTINOVA, Pavla VANKOVA, Alan KADEK, Charlotte UETRECHT, Haydyn MERTENS and Cyril BARINKA. In-solution structure and oligomerization of human histone deacetylase 6-an integrative approach. \textit{FEBS Journal}. MALDEN: Blackwell, 2023, vol.~290, No~3, p.~821-836. ISSN~1742-464X. Available from: https://dx.doi.org/10.1111/febs.16616.
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