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

PDB id:

5hq2

Name:

Transferase/DNA

Title:

Structural model of set8 histone h4 lys20 methyltransferase bound to nucleosome core particle

Structure:

Histone h3.2. Chain: a. Engineered: yes. Histone h4. Chain: b. Engineered: yes. Histone h2a. Chain: g. Engineered: yes.

Source:

Xenopus laevis. African clawed frog. Organism_taxid: 8355. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: hist1h2aj, loc494591. Synthetic construct. Organism_taxid: 32630. Gene: widom 601 nucleosome positioning sequence.

Resolution:

4.50Å R-factor: 0.342 R-free: 0.397

Authors:

G.Tavarekere,R.K.Mcginty,S.Tan

Key ref:

T.S.Girish et al. (2016). Multivalent Interactions by the Set8 Histone Methyltransferase With Its Nucleosome Substrate. J Mol Biol, 428, 1531-1543. PubMed id: 26953260 DOI: 10.1016/j.jmb.2016.02.025

Date:

21-Jan-16 Release date: 23-Mar-16

Protein chain

P84233  (H32_XENLA) -  Histone H3.2 from Xenopus laevis

Seq: 136 a.a.

Struc: 99 a.a.*

Protein chain

P62799  (H4_XENLA) -  Histone H4 from Xenopus laevis

Seq: 103 a.a.

Struc: 78 a.a.

Protein chain

P06897  (H2A1_XENLA) -  Histone H2A type 1 from Xenopus laevis

Seq: 130 a.a.

Struc: 105 a.a.*

Protein chain

P02281  (H2B11_XENLA) -  Histone H2B 1.1 from Xenopus laevis

Seq: 126 a.a.

Struc: 95 a.a.*

Protein chain

P21827  (RCC1_YEAST) -  Guanine nucleotide exchange factor SRM1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 482 a.a.

Struc: 422 a.a.

Protein chain

Q9NQR1  (KMT5A_HUMAN) -  N-lysine methyltransferase KMT5A from Homo sapiens

Seq: 393 a.a.

Struc: 160 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DNA/RNA chains

T-C-G-T-A-G-A-C-A-G-C-T-C-T-A-G-C-A-C-C-G-C-T-T-A-A-A-C-G-C-A-C-G-T-A-C-G-C-G- 73 bases

C-A-G-G-A-T-G-T-A-T-A-T-A-T-C-T-G-A-C-A-C-G-T-G-C-C-T-G-G-A-G-A-C-C-G-C-G-T-A- 72 bases

Enzyme reactions

• Enzyme class 1: Chain M: E.C.2.1.1.- - ?????
• Enzyme class 2: Chain M: E.C.2.1.1.361 - [histone H4]-lysine(20) N-methyltransferase.
• Reaction: L-lysyl₂₀-[histone H4] + S-adenosyl-L-methionine = N₆-methyl-L- lysyl₂₀-[histone H4] + S-adenosyl-L-homocysteine + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.jmb.2016.02.025

J Mol Biol 428:1531-1543 (2016)

PubMed id: 26953260

Multivalent Interactions by the Set8 Histone Methyltransferase With Its Nucleosome Substrate.

T.S.Girish, R.K.McGinty, S.Tan.

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.