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

J 2023

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

SHUKLA, Shivam; Jan KOMAREK; Zora NOVAKOVA; Jana NEDVEDOVA; Kseniya USTINOVA et. al.

Basic information

Original name

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

Authors

SHUKLA, Shivam; Jan KOMAREK; Zora NOVAKOVA; Jana NEDVEDOVA; Kseniya USTINOVA; Pavla VANKOVA; Alan KADEK; Charlotte UETRECHT; Haydyn MERTENS and Cyril BARINKA

Edition

FEBS Journal, MALDEN, Blackwell, 2023, 1742-464X

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 5.500

RIV identification code

RIV/00216224:90127/23:00136223

DOI

https://doi.org/10.1111/febs.16616

UT WoS

000855121600001

EID Scopus

2-s2.0-85138318680

Keywords in English

acetylation; analytical ultracentrifugation; intrinsically disordered regions; oligomerization; small-angle X-ray scattering

Abstract

In the original language

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.

Links

90127, large research infrastructures

Name: CIISB II

Cite

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. FEBS Journal. MALDEN: Blackwell, 2023, vol. 290, No 3, p. 821-836. ISSN 1742-464X. Available from: https://doi.org/10.1111/febs.16616.

@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 = {https://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://doi.org/10.1111/febs.16616.

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