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.

Základní údaje

Originální název

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

Autoři

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

Vydání

FEBS Journal, Hoboken, NJ USA, WILEY-BLACKWELL, 2023, 1742-464X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.400 v roce 2022

Organizační jednotka

Středoevropský technologický institut

DOI

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

UT WoS

000855121600001

Klíčová slova anglicky

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

Štítky

CF BIC, ne MU

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 16. 3. 2023 12:24, Mgr. Pavla Foltynová, Ph.D.

Anotace

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. Keywords

Návaznosti

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

SHUKLA, Shivam, Jan KOMAREK, Zora NOVAKOVA, Jana NEDVEDOVA, Kseniya USTINOVA, Pavla VANKOVA, Alan KADEK, Charlotte UETRECHT, Haydyn MERTENS a Cyril BARINKA. In-solution structure and oligomerization of human histone deacetylase 6-an integrative approach. FEBS Journal. Hoboken, NJ USA: WILEY-BLACKWELL, 2023, roč. 290, č. 3, s. 821-836. ISSN 1742-464X. Dostupné z: https://dx.doi.org/10.1111/febs.16616.

@article{2262568,
   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 = {Hoboken, NJ USA},
   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  - 2262568
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  - WILEY-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. Keywords
ER  -

SHUKLA, Shivam, Jan KOMAREK, Zora NOVAKOVA, Jana NEDVEDOVA, Kseniya USTINOVA, Pavla VANKOVA, Alan KADEK, Charlotte UETRECHT, Haydyn MERTENS a Cyril BARINKA. In-solution structure and oligomerization of human histone deacetylase 6-an integrative approach. \textit{FEBS Journal}. Hoboken, NJ USA: WILEY-BLACKWELL, 2023, roč.~290, č.~3, s.~821-836. ISSN~1742-464X. Dostupné z: https://dx.doi.org/10.1111/febs.16616.

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