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Molecular basis for the autoregulation of the protein acetyl transferase Rtt109

Stavropoulos, Pete and Nagy, Vivien and Blobel, Günter and Hoelz, André (2008) Molecular basis for the autoregulation of the protein acetyl transferase Rtt109. Proceedings of the National Academy of Sciences of the United States of America, 105 (34). pp. 12236-12241. ISSN 0027-8424. PMCID PMC2527895. doi:10.1073/pnas.0805813105.

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Rtt109 is a protein acetyltransferase (PAT) that is responsible for the acetylation of lysine-56 of histone 3 (H3K56) in yeast. H3K56 acetylation has been implicated in the weakening of the interaction between the histone core and the surrounding DNA in the nucleosomal particle. Rtt109, in cooperation with various histone chaperones, promotes genomic stability and is required for resistance to DNA damaging agents. Here, we present the crystal structure of Rtt109 in complex with acetyl-CoA at a 2.0-Å resolution. Rtt109 consists of a core PAT domain, which binds the acetyl-CoA cofactor. A second domain, the activation domain, is tightly associated with the PAT domain. Autoacetylation of lysine-290 within the activation domain is required for stabilizing the interaction between the two domains and is essential for catalysis. Biochemical analysis demonstrates the requirement of a loop within the PAT domain for the binding of the histone chaperone Vps75, and mutational analysis identifies key residues for catalysis. We propose a model in which the autoacetylation of Rtt109 is crucial for the regulation of its catalytic activity.

Item Type:Article
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URLURL TypeDescription Information CentralArticle
Hoelz, André0000-0003-1726-0127
Additional Information:© 2008 National Academy of Sciences. Contributed by Günter Blobel, June 18, 2008 (sent for review May 15, 2008). We thank A. Patke for discussions and comments on the manuscript, S. Etherton for help with editing the manuscript, M. Kampmann for advice on the yeast experiments, D. King for mass spectrometry analysis, T. Noriega for technical support, and B. Manjasetty and W. Shi for support during data collection. A.H. was supported by a grant from the Leukemia and Lymphoma Society. Author contributions: P.S. and A.H. designed research; P.S., V.N., and A.H. performed research; P.S., V.N., G.B., and A.H. analyzed data; and P.S. and A.H. wrote the paper. The authors declare no conflict of interest. Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, (PDB ID code 3CZ7). This article contains supporting information online at
Funding AgencyGrant Number
Leukemia and Lymphoma SocietyUNSPECIFIED
Subject Keywords:DNA repair; histone; structure
Issue or Number:34
PubMed Central ID:PMC2527895
Record Number:CaltechAUTHORS:20200407-095617796
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Official Citation:Molecular basis for the autoregulation of the protein acetyl transferase Rtt109. Pete Stavropoulos, Vivien Nagy, Günter Blobel, André Hoelz. Proceedings of the National Academy of Sciences Aug 2008, 105 (34) 12236-12241; DOI: 10.1073/pnas.0805813105
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102377
Deposited By: Tony Diaz
Deposited On:07 Apr 2020 17:54
Last Modified:16 Nov 2021 18:11

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