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

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.400 in 2022

DOI

http://dx.doi.org/10.1111/febs.16616

UT WoS

000855121600001

Keywords in English

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

Abstract

V originále

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

Citovat

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://dx.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 = {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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