The disordered N-terminus of HDAC6 is a microtubule-binding domain critical for efficient tubulin deacetylation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F20%3A00524504" target="_blank" >RIV/86652036:_____/20:00524504 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/20:10422299

Result on the web

<a href="https://www.jbc.org/content/295/9/2614.full#ack-1" target="_blank" >https://www.jbc.org/content/295/9/2614.full#ack-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.RA119.011243" target="_blank" >10.1074/jbc.RA119.011243</a>

Result language

angličtina

Original language name

The disordered N-terminus of HDAC6 is a microtubule-binding domain critical for efficient tubulin deacetylation

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

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Volume of the periodical

295

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

2614-2628

UT code for WoS article

000519969100008

EID of the result in the Scopus database

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