Structure of the Rtt109-AcCoA/Vps75 complex and implications for chaperone-mediated histone acetylation

Yong Tang, Marc A. Holbert, Neda Delgoshaie, Hugo Wurtele, Benoît Guillemette, Katrina Meeth, Hua Yuan, Paul Drogaris, Eun Hye Lee, Chantal Durette, Pierre Thibault, Alain Verreault, Philip A. Cole, Ronen Marmorstein

Research output: Contribution to journalArticle

Abstract

Yeast Rtt109 promotes nucleosome assembly and genome stability by acetylating K9, K27, and K56 of histone H3 through interaction with either of two distinct histone chaperones, Vps75 or Asf1. We report the crystal structure of an Rtt109-AcCoA/Vps75 complex revealing an elongated Vps75 homodimer bound to two globular Rtt109 molecules to form a symmetrical holoenzyme with a ∼12 diameter central hole. Vps75 and Rtt109 residues that mediate complex formation in the crystals are also important for Rtt109-Vps75 interaction and H3K9/K27 acetylation both in vitro and in yeast cells. The same Rtt109 residues do not participate in Asf1-mediated Rtt109 acetylation in vitro or H3K56 acetylation in yeast cells, demonstrating that Asf1 and Vps75 dictate Rtt109 substrate specificity through distinct mechanisms. These studies also suggest that Vps75 binding stimulates Rtt109 catalytic activity by appropriately presenting the H3-H4 substrate within the central cavity of the holoenzyme to promote H3K9/K27 acetylation of new histones before deposition.

Original languageEnglish (US)
Pages (from-to)221-231
Number of pages11
JournalStructure
Volume19
Issue number2
DOIs
StatePublished - Feb 9 2011

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Histone Chaperones
Acetylation
Holoenzymes
Yeasts
Histones
Nucleosomes
Genomic Instability
Substrate Specificity

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Tang, Y., Holbert, M. A., Delgoshaie, N., Wurtele, H., Guillemette, B., Meeth, K., ... Marmorstein, R. (2011). Structure of the Rtt109-AcCoA/Vps75 complex and implications for chaperone-mediated histone acetylation. Structure, 19(2), 221-231. https://doi.org/10.1016/j.str.2010.12.012

Structure of the Rtt109-AcCoA/Vps75 complex and implications for chaperone-mediated histone acetylation. / Tang, Yong; Holbert, Marc A.; Delgoshaie, Neda; Wurtele, Hugo; Guillemette, Benoît; Meeth, Katrina; Yuan, Hua; Drogaris, Paul; Lee, Eun Hye; Durette, Chantal; Thibault, Pierre; Verreault, Alain; Cole, Philip A.; Marmorstein, Ronen.

In: Structure, Vol. 19, No. 2, 09.02.2011, p. 221-231.

Research output: Contribution to journalArticle

Tang, Y, Holbert, MA, Delgoshaie, N, Wurtele, H, Guillemette, B, Meeth, K, Yuan, H, Drogaris, P, Lee, EH, Durette, C, Thibault, P, Verreault, A, Cole, PA & Marmorstein, R 2011, 'Structure of the Rtt109-AcCoA/Vps75 complex and implications for chaperone-mediated histone acetylation', Structure, vol. 19, no. 2, pp. 221-231. https://doi.org/10.1016/j.str.2010.12.012
Tang Y, Holbert MA, Delgoshaie N, Wurtele H, Guillemette B, Meeth K et al. Structure of the Rtt109-AcCoA/Vps75 complex and implications for chaperone-mediated histone acetylation. Structure. 2011 Feb 9;19(2):221-231. https://doi.org/10.1016/j.str.2010.12.012
Tang, Yong ; Holbert, Marc A. ; Delgoshaie, Neda ; Wurtele, Hugo ; Guillemette, Benoît ; Meeth, Katrina ; Yuan, Hua ; Drogaris, Paul ; Lee, Eun Hye ; Durette, Chantal ; Thibault, Pierre ; Verreault, Alain ; Cole, Philip A. ; Marmorstein, Ronen. / Structure of the Rtt109-AcCoA/Vps75 complex and implications for chaperone-mediated histone acetylation. In: Structure. 2011 ; Vol. 19, No. 2. pp. 221-231.
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