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
Typ výsledku
Článek v odborném periodiku
Obor
10608 Biochemistry and molecular biology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 5.400 v roce 2022
Organizační jednotka
Středoevropský technologický institut
Klíčová slova anglicky
acetylation; analytical ultracentrifugation; intrinsically disordered regions; oligomerization; small-angle X-ray scattering
Příznaky
Mezinárodní význam, Recenzováno
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
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Zobrazeno: 5. 11. 2024 06:14