Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet.

Journal Article · Wed Jan 15 04:00:00 EST 2003 · EMBO J.

DOI:https://doi.org/10.1093/emboj/cdg025· OSTI ID:961187

Kwon, T; Chang, J H; Kwak, E; Lee, C W; Joachimiak, A; Kim, Y C; Lee, J; Cho, Y

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 {angstrom} 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.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: FOR
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 961187
• Report Number(s): ANL/BIO/JA-45335
• Journal Information: EMBO J., Journal Name: EMBO J. Journal Issue: 2 ; Jan. 15, 2003 Vol. 22; ISSN EMJODG; ISSN 0261-4189
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CHROMATIN
CRYSTAL STRUCTURE
DISSOCIATION
GENES
HISTONES
LYSINE
METHYLATION
MOLECULES
REGULATIONS
RESIDUES
RESOLUTION
SUBSTRATES
TYROSINE