3RC0: Human Setd6 In Complex With Rela Lys310 Peptide

Citation:
Abstract
SET domain containing 6 (SETD6) monomethylates the RelA subunit of nuclear factor kappa B (NF-kappaB). 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-kappaB 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.
PDB ID: 3RC0Download
MMDB ID: 90862
PDB Deposition Date: 2011/3/30
Updated in MMDB: 2011/09
Experimental Method:
x-ray diffraction
Resolution: 2.19  Å
Source Organism:
Similar Structures:
Biological Unit for 3RC0: dimeric; determined by author and by software (PISA)
Molecular Components in 3RC0
Label Count Molecule
Proteins (2 molecules)
1
N-lysine Methyltransferase Setd6(Gene symbol: SETD6)
Molecule annotation
1
Transcription Factor P65 Peptide(Gene symbol: RELA)
Molecule annotation
Chemicals (10 molecules)
1
9
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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