Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9–AdoMet
AUTOR(ES)
Kwon, Taewoo
FONTE
Oxford University Press
RESUMO
The methylation of lysine residues of histones plays a pivotal role in the regulation of chromatin structure and gene expression. Here, we report two crystal structures of SET7/9, a histone methyltransferase (HMTase) that transfers methyl groups to Lys4 of histone H3, in complex with S-adenosyl-l-methionine (AdoMet) determined at 1.7 and 2.3 Å resolution. The structures reveal an active site consisting of: (i) a binding pocket between the SET domain and a c-SET helix where an AdoMet molecule in an unusual conformation binds; (ii) a narrow substrate-specific channel that only unmethylated lysine residues can access; and (iii) a catalytic tyrosine residue. The methyl group of AdoMet is directed to the narrow channel where a substrate lysine enters from the opposite side. We demonstrate that SET7/9 can transfer two but not three methyl groups to unmodified Lys4 of H3 without substrate dissociation. The unusual features of the SET domain-containing HMTase discriminate between the un- and methylated lysine substrate, and the methylation sites for the histone H3 tail.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=140100Documentos Relacionados
- AdoMet radical proteins—from structure to evolution—alignment of divergent protein sequences reveals strong secondary structure element conservation
- Probing a rate-limiting step by mutational perturbation of AdoMet binding in the HhaI methyltransferase
- A locking mechanism preventing radical damage in the absence of substrate, as revealed by the x-ray structure of lysine 5,6-aminomutase
- Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: A potential mechanism for position-effect variegation
- The histone 3 lysine 36 methyltransferase, SET2, is involved in transcriptional elongation