3RC0

Human SETD6 in complex with RelA Lys310 peptide

3RC0 の概要

• エントリーDOI: 10.2210/pdb3rc0/pdb
• 関連するPDBエントリー: 3QXY
• 分子名称: N-lysine methyltransferase SETD6, Transcription factor p65 peptide, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: epigenetics, protein lysine monomethylation, mammalian nuclear factor kb (nf-kb), transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q8TBK2 Q04206
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 107284.19

構造登録者

Chang, Y.,Levy, D.,Horton, J.R.,Peng, J.,Zhang, X.,Gozani, O.,Cheng, X. (登録日: 2011-03-30, 公開日: 2011-05-25, 最終更新日: 2023-09-13)

主引用文献

Chang, Y.,Levy, D.,Horton, J.R.,Peng, J.,Zhang, X.,Gozani, O.,Cheng, X.
Structural basis of SETD6-mediated regulation of the NF-kB network via methyl-lysine signaling.
Nucleic Acids Res., 39:6380-6389, 2011

PubMed Abstract: SET domain containing 6 (SETD6) monomethylates the RelA subunit of nuclear factor kappa B (NF-κB). The ankyrin repeats of G9a-like protein (GLP) recognizes RelA monomethylated at Lys310. Adjacent to Lys310 is Ser311, a known phosphorylation site of RelA. Ser311 phosphorylation inhibits Lys310 methylation by SETD6 as well as binding of Lys310me1 by GLP. The structure of SETD6 in complex with RelA peptide containing the methylation site, in the presence of S-adenosyl-L-methionine, reveals a V-like protein structure and suggests a model for NF-κB binding to SETD6. In addition, structural modeling of the GLP ankyrin repeats bound to Lys310me1 peptide provides insight into the molecular basis for inhibition of Lys310me1 binding by Ser311 phosphorylation. Together, these findings provide a structural explanation for a key cellular signaling pathway centered on RelA Lys310 methylation, which is generated by SETD6 and recognized by GLP, and incorporate a methylation-phosphorylation switch of adjacent lysine and serine residues. Finally, SETD6 is structurally similar to the Rubisco large subunit methyltransferase. Given the restriction of Rubisco to plant species, this particular appearance of the protein lysine methyltransferase has been evolutionarily well conserved.

PubMed: 21515635
DOI: 10.1093/nar/gkr256

実験手法

X-RAY DIFFRACTION (2.19 Å)