Structure of the SET domain histone lysine methyltransferase Clr4.
Methylation of histone H3 lysine 9 is an important component of the 'histone code' for heterochromatic gene silencing. The SET domain-containing Clr4 protein, a close relative of Su(var)3-9 proteins in higher eukaryotes, specifically methylates lysine 9 of histone H3 and is essential for silencing in Schizosaccharomyces pombe. Here we report the 2.3 A resolution crystal structure of the catalytic domain of Clr4. The structure reveals an overall fold rich in beta-strands, a potential active site consisting of a SAM-binding pocket, and a connected groove that could accommodate the binding of the N-terminal tail of histone H3. The pre-SET motif contains a triangular zinc cluster coordinated by nine cysteines distant from the active site, whereas the post-SET region is largely flexible but proximal to the active site. The structure provides insights into the architecture of SET domain histone methyltransferases and establishes a paradigm for further characterization of the Clr4 family of epigenetic regulators.
Min
Jinrong
J
W.M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Zhang
Xing
X
Cheng
Xiaodong
X
Grewal
Shiv I S
SI
Xu
Rui-Ming
RM
D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008780:Methyltransferases; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000737:chemistry; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry*; D016415:Sequence Alignment
D018797:Cell Cycle Proteins; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C112744:clr4 protein, S pombe; D008239:Lysine