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
Zobrazeno: 5. 11. 2024 06:14