PDBsum entry 5fb1

Transcription/structural protein

PDB id: 5fb1

Contents

Protein chain

174 a.a.

Ligands

ALA-ARG-THR-LYS-GLN-THR-ALA-ARG

MLI

Metals

_ZN ×2

Waters ×155

PDB id:

5fb1

Name:

Transcription/structural protein

Title:

Crystal structure of a phd finger bound to histone h3 k9me3 peptide

Structure:

Nuclear autoantigen sp-100. Chain: a. Fragment: unp residues 696-878. Synonym: sp100 nuclear antigen. Engineered: yes. Mutation: yes. Peptide from histone h3. Chain: c. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sp100. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: chemically synthesized h3 peptide 1-15 with k9me3 modification

Resolution:

2.10Å R-factor: 0.169 R-free: 0.220

Authors:

H.Li,X.Zhang

Key ref:

X.Zhang et al. (2016). Multifaceted Histone H3 Methylation and Phosphorylation Readout by the Plant Homeodomain Finger of Human Nuclear Antigen Sp100C. J Biol Chem, 291, 12786-12798. PubMed id: 27129259 DOI: 10.1074/jbc.M116.721159

Date:

13-Dec-15 Release date: 04-May-16

Protein chain

P23497  (SP100_HUMAN) -  Nuclear autoantigen Sp-100 from Homo sapiens

Seq: 879 a.a.

Struc: 174 a.a.*

* PDB and UniProt seqs differ at 151 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M116.721159

J Biol Chem 291:12786-12798 (2016)

PubMed id: 27129259

Multifaceted Histone H3 Methylation and Phosphorylation Readout by the Plant Homeodomain Finger of Human Nuclear Antigen Sp100C.

X.Zhang, D.Zhao, X.Xiong, Z.He, H.Li.

ABSTRACT

The decoding of histone post-translational modifications by chromatin-binding modules ("readers") constitutes one major mechanism of epigenetic regulation. Nuclear antigen Sp100 (SPECKLED, 100 kDa), a constitutive component of the promyelocytic leukemia nuclear bodies, plays key roles in intrinsic immunity and transcriptional repression. Sp100C, a splicing isoform specifically up-regulated upon interferon stimulation, harbors a unique tandem plant homeodomain (PHD) finger and bromodomain at its C terminus. Combining structural, quantitative binding, and cellular co-localization studies, we characterized Sp100C PHD finger as an unmethylated histone H3 Lys(4) (H3K4me0) reader that tolerates histone H3 Thr(3) phosphorylation (H3T3ph), histone H3 Lys(9) trimethylation (H3K9me3), and histone H3 Ser(10) phosphorylation (H3S10ph), hallmarks associated with the mitotic chromosome. In contrast, whereas H3K4me0 reader activity is conserved in Sp140, an Sp100C paralog, the multivalent tolerance of H3T3ph, H3K9me3, and H3S10ph was lost for Sp140. The complex structure determined at 2.1 Å revealed a highly coordinated lysine ϵ-amine recognition sphere formed by an extended N-terminal motif for H3K4me0 readout. Interestingly, reader pocket rigidification by disulfide bond formation enhanced H3K4me0 binding by Sp100C. An additional complex structure solved at 2.7 Å revealed that H3T3ph is recognized by the arginine residue, Arg(713), that is unique to the PHD finger of Sp100C. Consistent with a restrictive cellular role of Sp100C, these results establish a direct chromatin targeting function of Sp100C that may regulate transcriptional gene silencing and promyelocytic leukemia nuclear body-mediated intrinsic immunity in response to interferon stimulation.