Histone chaperone specificity in Rtt109 activation.
Rtt109 is a histone acetyltransferase that requires a histone chaperone for the acetylation of histone 3 at lysine 56 (H3K56). Rtt109 forms a complex with the chaperone Vps75 in vivo and is implicated in DNA replication and repair. Here we show that both Rtt109 and Vps75 bind histones with high affinity, but only the complex is efficient for catalysis. The C-terminal acidic domain of Vps75 contributes to activation of Rtt109 and is necessary for in vivo functionality of Vps75, but it is not required for interaction with either Rtt109 or histones. We demonstrate that Vps75 is a structural homolog of yeast Nap1 by solving its crystal structure. Nap1 and Vps75 interact with histones and Rtt109 with comparable affinities. However, only Vps75 stimulates Rtt109 enzymatic activity. Our data highlight the functional specificity of Vps75 in Rtt109 activation.
Park
Young-Jun
YJ
Howard Hughes Medical Institute, Colorado State University, Fort Collins, Colorado 80523-1870, USA.
Sudhoff
Keely B
KB
Andrews
Andrew J
AJ
Stargell
Laurie A
LA
Luger
Karolin
K
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005800:Genes, Fungal; D051548:Histone Acetyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances / Q000737:chemistry; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D056490:Nucleosome Assembly Protein 1; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D018797:Cell Cycle Proteins; D006657:Histones; D046911:Macromolecular Substances; D018832:Molecular Chaperones; C533556:NAP1 protein, S cerevisiae; D009687:Nuclear Proteins; D056490:Nucleosome Assembly Protein 1; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C525548:Vps75 protein, S cerevisiae; D051548:Histone Acetyltransferases; C517120:Rtt109 protein, S cerevisiae