5HQ2

Structural model of Set8 histone H4 Lys20 methyltransferase bound to nucleosome core particle

Summary for 5HQ2

• Entry DOI: 10.2210/pdb5hq2/pdb
• Descriptor: Histone H3.2, Histone H4, Histone H2A, ... (8 entities in total)
• Functional Keywords: chromatin enzyme, chromatin complex, epigenetics, histone methyltransferase, transferase-dna complex, transferase/dna
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 8
• Total formula weight: 222166.63

Authors

Tavarekere, G.,McGinty, R.K.,Tan, S. (deposition date: 2016-01-21, release date: 2016-03-23, Last modification date: 2024-03-06)

Primary citation

Girish, T.S.,McGinty, R.K.,Tan, S.
Multivalent Interactions by the Set8 Histone Methyltransferase With Its Nucleosome Substrate.
J.Mol.Biol., 428:1531-1543, 2016

PubMed 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.

PubMed: 26953260
DOI: 10.1016/j.jmb.2016.02.025

Experimental method

X-RAY DIFFRACTION (4.5 Å)