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Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBP.

Nature structural & molecular biology | 2008

Rtt109, also known as KAT11, is a recently characterized fungal-specific histone acetyltransferase (HAT) that modifies histone H3 lysine 56 (H3K56) to promote genome stability. Rtt109 does not show sequence conservation with other known HATs and depends on association with either of two histone chaperones, Asf1 or Vps75, for HAT activity. Here we report the X-ray crystal structure of an Rtt109-acetyl coenzyme A complex and carry out structure-based mutagenesis, combined with in vitro biochemical studies of the Rtt109-Vps75 complex and studies of Rtt109 function in vivo. The Rtt109 structure reveals noteworthy homology to the metazoan p300/CBP HAT domain but exhibits functional divergence, including atypical catalytic properties and mode of cofactor regulation. The structure reveals a buried autoacetylated lysine residue that we show is also acetylated in the Rtt109 protein purified from yeast cells. Implications for understanding histone substrate and chaperone binding by Rtt109 are discussed.

Pubmed ID: 18568037 RIS Download

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060293-04
  • Agency: NCRR NIH HHS, United States
    Id: U54 RR020839
  • Agency: NCRR NIH HHS, United States
    Id: U54 RR020839-028117
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060293-02
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060293-08
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM062437-06
  • Agency: NCRR NIH HHS, United States
    Id: U54 RR020839-036286
  • Agency: NIA NIH HHS, United States
    Id: P01 AG031862
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060293-06
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060293-07
  • Agency: NIGMS NIH HHS, United States
    Id: Y1 GM-0080-03
  • Agency: NCRR NIH HHS, United States
    Id: U54 RR020839-045925
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060293-03
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060293-01
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM062437-05
  • Agency: NIGMS NIH HHS, United States
    Id: Y01 GM000080
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM062437-08S1
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060293-05
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM062437
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM062437-07
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM062437-08
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060293

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Refmac (tool)

RRID:SCR_014225

A molecular refinement program with two main modes: REVIEW, which checks and updates the input model to establish that the geometric restraints can be properly set up, and REFINE mode, which is the standard mode and documented in keywords. In REVIEW users can: check model coordinates and write an extended output set of coordinates, find disulphide bonds and other covalent links, cis-peptides, output the sequence and REMARK records. In REFINEMENT mode users can carry out rigid body, tls, restrained or unrestrained refinement against Xray data, or idealisation of a macromolecular structure. Also in REFINEMENT mode, Refmac produces an MTZ output file containing weighted coefficients for SigmaA weighted mFo-DFcalc and 2mFo-DFcalc maps. The program is supported by CCP4.

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