title: Structural insights into histone H3 lysine 56 acetylation by Rtt109.
abstract: Histone acetylation plays important roles for the regulation of many fundamental cellular processes. Saccharomyces cerevisiae Rtt109 is an important class of histone acetyltransferases (HATs), which promote genome stability by directly acetylating newly synthesized histone H3 lysine 56 (H3-K56) through an unknown mechanism. Here, we report the crystal structures of Rtt109 at 2.2 A and Rtt109/Acetyl-CoA binary complex at 1.9 A. The structure displays a vise-like topology with mixed three-layered alpha/beta module forming the central module, whose core region resembles the structure of GCN5 HAT domain and P300/CBP HAT domain. Using structural and biochemical analyses, we have discovered the catalytic active site and have identified Asp288 as the deprotonation residue and Lys290 as the autoacetylation residue. We have further proposed the unique H3-K56 anchoring pocket and the potential H3alphaN binding groove. Our work has provided structural insights to understand the acetylation mechanism of H3-K56 by Rtt109.
authors: Genome and Structural Biology Program, Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, Singapore.
authors: Chengqi
authors: C
authors: Lin
authors: Y Adam
authors: YA
authors: Yuan
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases; C517120:Rtt109 protein, S cerevisiae; D008239:Lysine