PDBsum entry 4psx

Histone/transferase

PDB id: 4psx

Contents

Protein chains

313 a.a.

361 a.a.

39 a.a.

37 a.a.

12 a.a.

Ligands

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

COA ×2

SO4

Waters ×606

PDB id:

4psx

Name:

Histone/transferase

Title:

Crystal structure of histone acetyltransferase complex

Structure:

Histone acetyltransferase type b catalytic subunit. Chain: a, d. Fragment: unp residues 7-319. Engineered: yes. Histone acetyltransferase type b subunit 2. Chain: b, e. Fragment: unp residues 8-389. Engineered: yes. Mutation: yes.

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 559292. Strain: atcc 204508 / s288c. Gene: hat1, lpa16w, yp8132.12, ypl001w. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: hat2, yel056w. Expressed in: spodoptera frugiperda.

Resolution:

2.51Å R-factor: 0.183 R-free: 0.223

Authors:

M.Yang,Y.Li

Key ref:

Y.Li et al. (2014). Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex. Genes Dev, 28, 1217-1227. PubMed id: 24835250 DOI: 10.1101/gad.240531.114

Date:

08-Mar-14 Release date: 09-Jul-14

Protein chains

Q12341  (HAT1_YEAST) -  Histone acetyltransferase type B catalytic subunit from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 374 a.a.

Struc: 313 a.a.

Protein chains

P39984  (HAT2_YEAST) -  Histone acetyltransferase type B subunit 2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 401 a.a.

Struc: 361 a.a.*

Protein chain

P02309  (H4_YEAST) -  Histone H4 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 103 a.a.

Struc: 39 a.a.*

Protein chain

P02309  (H4_YEAST) -  Histone H4 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 103 a.a.

Struc: 37 a.a.*

Protein chain

P61830  (H3_YEAST) -  Histone H3 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 136 a.a.

Struc: 12 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, D: E.C.2.3.1.48 - histone acetyltransferase.
• Reaction: L-lysyl-[protein] + acetyl-CoA = N₆-acetyl-L-lysyl-[protein] + CoA + H⁺

L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] (Bound ligand (Het Group name = COA) corresponds exactly) + CoA + H(+)

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

Added reference

DOI no: 10.1101/gad.240531.114

Genes Dev 28:1217-1227 (2014)

PubMed id: 24835250

Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex.

Y.Li, L.Zhang, T.Liu, C.Chai, Q.Fang, H.Wu, P.A.Agudelo Garcia, Z.Han, S.Zong, Y.Yu, X.Zhang, M.R.Parthun, J.Chai, R.M.Xu, M.Yang.

ABSTRACT

Post-translational modifications of histones are significant regulators of replication, transcription, and DNA repair. Particularly, newly synthesized histone H4 in H3/H4 heterodimers becomes acetylated on N-terminal lysine residues prior to its incorporation into chromatin. Previous studies have established that the histone acetyltransferase (HAT) complex Hat1p/Hat2p medicates this modification. However, the mechanism of how Hat1p/Hat2p recognizes and facilitates the enzymatic activities on the newly assembled H3/H4 heterodimer remains unknown. Furthermore, Hat2p is a WD40 repeat protein, which is found in many histone modifier complexes. However, how the WD40 repeat proteins facilitate enzymatic activities of histone modification enzymes is unclear. In this study, we first solved the high-resolution crystal structure of a Hat1p/Hat2p/CoA/H4 peptide complex and found that the H4 tail interacts with both Hat1p and Hat2p, by which substrate recruitment is facilitated. We further discovered that H3 N-terminal peptides can bind to the Hat2p WD40 domain and solved the structure of the Hat1p/Hat2p/CoA/H4/H3 peptide complex. Moreover, the interaction with Hat2p requires unmodified Arg2/Lys4 and Lys9 on the H3 tail, suggesting a novel model to specify the activity of Hat1p/Hat2p toward newly synthesized H3/H4 heterodimers. Together, our study demonstrated the substrate recognition mechanism by the Hat1p/Hat2p complex, which is critical for DNA replication and other chromatin remodeling processes.