Structural and functional analyses of methyl-lysine binding by the malignant brain tumour repeat protein Sex comb on midleg.
Sex comb on midleg (Scm) is a member of the Polycomb group of proteins involved in the maintenance of repression of Hox and other developmental control genes in Drosophila. The two malignant brain tumour (MBT) repeats of Scm form a domain that preferentially binds to monomethylated lysine residues either as a free amino acid or in the context of peptides, while unmodified or di- or trimethylated lysine residues are bound with significantly lower affinity. The crystal structure of a monomethyl-lysine-containing histone tail peptide bound to the MBT repeat domain shows that the methyl-lysine side chain occupies a binding pocket in the second MBT repeat formed by three conserved aromatic residues and one aspartate. Insertion of the monomethylated side chain into this pocket seems to be the main contributor to the binding affinity. Functional analyses in Drosophila show that the MBT domain of Scm and its methyl-lysine-binding activity are required for repression of Hox genes.
Grimm
Clemens
C
European Molecular Biology Laboratory, Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble, France.
de Ayala Alonso
Andres Gaytan
AG
Rybin
Vladimir
V
Steuerwald
Ulrich
U
Ly-Hartig
Nga
N
Fischle
Wolfgang
W
Müller
Jürg
J
Müller
Christoph W
CW
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D019076:Transgenes
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; C066770:Pc protein, Drosophila; D010455:Peptides; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; C099357:SCM protein, Drosophila; D063150:Polycomb Repressive Complex 1; D008239:Lysine