PDBsum entry 5hq2

Transferase/DNA

PDB id: 5hq2

Contents

Protein chains

99 a.a.

78 a.a.

105 a.a.

95 a.a.

422 a.a.

160 a.a.

DNA/RNA

References listed in PDB file

Key reference

• Title: Multivalent interactions by the set8 histone methyltransferase with its nucleosome substrate.
• Authors: T.S.Girish, R.K.Mcginty, S.Tan.
• Ref.: J Mol Biol, 2016, 428, 1531-1543. [DOI no: 10.1016/j.jmb.2016.02.025]
• PubMed id: 26953260

Abstract

Set8 is the only mammalian monomethyltransferase responsible for H4K20me1, a methyl mark critical for genomic integrity of eukaryotic cells. We present here a structural model for how Set8 uses multivalent interactions to bind and methylate the nucleosome based on crystallographic and solution studies of the Set8/nucleosome complex. Our studies indicate that Set8 employs its i-SET and c-SET domains to engage nucleosomal DNA 1 to 1.5 turns from the nucleosomal dyad and in doing so, it positions the SET domain for catalysis with H4 Lys20. Surprisingly, we find that a basic N-terminal extension to the SET domain plays an even more prominent role in nucleosome binding, possibly by making an arginine anchor interaction with the nucleosome H2A/H2B acidic patch. We further show that proliferating cell nuclear antigen and the nucleosome compete for binding to Set8 through this basic extension, suggesting a mechanism for how nucleosome binding protects Set8 from proliferating cell nuclear antigen-dependent degradation during the cell cycle.