Počet záznamů: 1
The disordered N-terminus of HDAC6 is a microtubule-binding domain critical for efficient tubulin deacetylation
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SYSNO ASEP 0524504 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název The disordered N-terminus of HDAC6 is a microtubule-binding domain critical for efficient tubulin deacetylation Tvůrce(i) Ustinova, Kseniya (BTO-N)
Nováková, Zora (BTO-N) ORCID, RID
Saito, M. (CH)
Meleshin, M. (DE)
Mikesova, Jana (BTO-N)
Kutil, Zsofia (BTO-N) RID, ORCID
Baranová, Petra (BTO-N)
Havlínová, Barbora (BTO-N)
Schutkowski, M. (DE)
Matthias, P. (CH)
Bařinka, Cyril (BTO-N) RID, ORCIDCelkový počet autorů 11 Zdroj.dok. Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 295, č. 9 (2020), s. 2614-2628Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova structure-function ; protein-protein interaction ; substrate specificity Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology CEP LM2015062 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy GA15-19640S GA ČR - Grantová agentura ČR LM2015043 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora BTO-N - RVO:86652036 UT WOS 000519969100008 DOI 10.1074/jbc.RA119.011243 Anotace Histone deacetylase 6 (HDAC6) is a multidomain cytosolic enzyme having tubulin deacetylase activity that has been unequivocally assigned to the second of the tandem catalytic domains. However, virtually no information exists on the contribution of other HDAC6 domains on tubulin recognition. Here, using recombinant protein expression, site-directed mutagenesis, fluorimetric and biochemical assays, microscale thermophoresis, and total internal reflection fluorescence microscopy, we identified the N-terminal, disordered region of HDAC6 as a microtubule-binding domain and functionally characterized it to the single-molecule level. We show that the microtubule-binding motif spans two positively charged patches comprising residues Lys-32 to Lys-58. We found that HDAC6-microtubule interactions are entirely independent of the catalytic domains and are mediated by ionic interactions with the negatively charged microtubule surface. Importantly, a crosstalk between the microtubule-binding domain and the deacetylase domain was critical for recognition and efficient deacetylation of free tubulin dimers both in vitro and in vivo. Overall, our results reveal that recognition of substrates by HDAC6 is more complex than previously appreciated and that domains outside the tandem catalytic core are essential for proficient substrate deacetylation. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2021 Elektronická adresa https://www.jbc.org/content/295/9/2614.full#ack-1
Počet záznamů: 1