Histone chaperone exploits intrinsic disorder to switch acetylation specificity

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Nataliya Danilenko
  • Lukas Lercher
  • John Kirkpatrick
  • Frank Gabel
  • Luca Codutti
  • Teresa Carlomagno

Externe Organisationen

  • Université Grenoble Alpes (UGA)
  • Institut Laue-Langevin
  • Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
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Details

OriginalspracheEnglisch
Aufsatznummer3435
Seitenumfang11
FachzeitschriftNature Communications
Jahrgang10
Frühes Online-Datum6 Aug. 2019
PublikationsstatusElektronisch veröffentlicht (E-Pub) - 6 Aug. 2019

Abstract

Histones, the principal protein components of chromatin, contain long disordered sequences, which are extensively post-translationally modified. Although histone chaperones are known to control both the activity and specificity of histone-modifying enzymes, the mechanisms promoting modification of highly disordered substrates, such as lysine-acetylation within the N-terminal tail of histone H3, are not understood. Here, to understand how histone chaperones Asf1 and Vps75 together promote H3 K9-acetylation, we establish the solution structural model of the acetyltransferase Rtt109 in complex with Asf1 and Vps75 and the histone dimer H3:H4. We show that Vps75 promotes K9-acetylation by engaging the H3 N-terminal tail in fuzzy electrostatic interactions with its disordered C-terminal domain, thereby confining the H3 tail to a wide central cavity faced by the Rtt109 active site. These fuzzy interactions between disordered domains achieve localization of lysine residues in the H3 tail to the catalytic site with minimal loss of entropy, and may represent a common mechanism of enzymatic reactions involving highly disordered substrates.

ASJC Scopus Sachgebiete

Zitieren

Histone chaperone exploits intrinsic disorder to switch acetylation specificity. / Danilenko, Nataliya; Lercher, Lukas; Kirkpatrick, John et al.
in: Nature Communications, Jahrgang 10, 3435, 06.08.2019.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Danilenko, N., Lercher, L., Kirkpatrick, J., Gabel, F., Codutti, L., & Carlomagno, T. (2019). Histone chaperone exploits intrinsic disorder to switch acetylation specificity. Nature Communications, 10, Artikel 3435. Vorabveröffentlichung online. https://doi.org/10.1038/s41467-019-11410-7, https://doi.org/10.15488/9281
Danilenko N, Lercher L, Kirkpatrick J, Gabel F, Codutti L, Carlomagno T. Histone chaperone exploits intrinsic disorder to switch acetylation specificity. Nature Communications. 2019 Aug 6;10:3435. Epub 2019 Aug 6. doi: 10.1038/s41467-019-11410-7, 10.15488/9281
Danilenko, Nataliya ; Lercher, Lukas ; Kirkpatrick, John et al. / Histone chaperone exploits intrinsic disorder to switch acetylation specificity. in: Nature Communications. 2019 ; Jahrgang 10.
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abstract = "Histones, the principal protein components of chromatin, contain long disordered sequences, which are extensively post-translationally modified. Although histone chaperones are known to control both the activity and specificity of histone-modifying enzymes, the mechanisms promoting modification of highly disordered substrates, such as lysine-acetylation within the N-terminal tail of histone H3, are not understood. Here, to understand how histone chaperones Asf1 and Vps75 together promote H3 K9-acetylation, we establish the solution structural model of the acetyltransferase Rtt109 in complex with Asf1 and Vps75 and the histone dimer H3:H4. We show that Vps75 promotes K9-acetylation by engaging the H3 N-terminal tail in fuzzy electrostatic interactions with its disordered C-terminal domain, thereby confining the H3 tail to a wide central cavity faced by the Rtt109 active site. These fuzzy interactions between disordered domains achieve localization of lysine residues in the H3 tail to the catalytic site with minimal loss of entropy, and may represent a common mechanism of enzymatic reactions involving highly disordered substrates.",
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AU - Codutti, Luca

AU - Carlomagno, Teresa

N1 - Funding Information: We thank ILL (D22 BAG system, BAG8-34, BAG8-36) and JCNS-MLZ (KWS-1 beam-time) for the SANS experiments; Dr. A. Martel (ILL, Grenoble) and Dr. A. Feoktystov (JCNS-MLZ, Garching) for help with the instrumental setup and SANS data collection. L. L. acknowledges the receipt of an EMBO Long-term Fellowship (ALTF 1474-2014, Marie Curie Actions, LTFCOFUND2013, GA-2103-609409).

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