PDBsum entry 1eqf

Transcription

PDB id: 1eqf

Contents

Protein chain

267 a.a. *

Ligands

SO4

Waters ×161

* Residue conservation analysis

PDB id:

1eqf

Name:

Transcription

Title:

Crystal structure of the double bromodomain module from human tafii250

Structure:

RNA polymerase ii transcription initiation factor. Chain: a. Fragment: double bromodomain, residues 1359-1638. Synonym: tafii250. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.218 R-free: 0.246

Authors:

R.H.Jacobson,A.G.Ladurner,D.S.King,R.Tjian

Key ref:

R.H.Jacobson et al. (2000). Structure and function of a human TAFII250 double bromodomain module. Science, 288, 1422-1425. PubMed id: 10827952 DOI: 10.1126/science.288.5470.1422

Date:

04-Apr-00 Release date: 07-Jun-00

Protein chain

P21675  (TAF1_HUMAN) -  Transcription initiation factor TFIID subunit 1 from Homo sapiens

Seq: 1893 a.a.

Struc: 267 a.a.

Enzyme reactions

• Enzyme class 1: E.C.2.3.1.48 - histone acetyltransferase.
• Reaction: L-lysyl-[protein] + acetyl-CoA = N₆-acetyl-L-lysyl-[protein] + CoA + H⁺
• Enzyme class 2: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + 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

reference

DOI no: 10.1126/science.288.5470.1422

Science 288:1422-1425 (2000)

PubMed id: 10827952

Structure and function of a human TAFII250 double bromodomain module.

R.H.Jacobson, A.G.Ladurner, D.S.King, R.Tjian.

ABSTRACT

TFIID is a large multiprotein complex that initiates assembly of the transcription machinery. It is unclear how TFIID recognizes promoters in vivo when templates are nucleosome-bound. Here, it is shown that TAFII250, the largest subunit of TFIID, contains two tandem bromodomain modules that bind selectively to multiply acetylated histone H4 peptides. The 2.1 angstrom crystal structure of the double bromodomain reveals two side-by-side, four-helix bundles with a highly polarized surface charge distribution. Each bundle contains an Nepsilon-acetyllysine binding pocket at its center, which results in a structure ideally suited for recognition of diacetylated histone H4 tails. Thus, TFIID may be targeted to specific chromatin-bound promoters and may play a role in chromatin recognition.

Selected figure(s)

Figure 3.
Fig. 3. Electrostatic charge distribution and binding pockets. Delphi electrostatic potential calculated and mapped onto the Connelly solvent accessible surface using InsightII calculated with coordinates corresponding to the core domain (residues 1379 to 1625). Simulated ionic strength was set to 0.145 M with a bulk solvent dielectric constant of 80. The first seven NH[2]-terminal residues from a symmetry-equivalent molecule are shown as a green stick model. The first three residues (1359 to 1361) are visible binding into the putative acetyllysine recognition pocket of the first domain. (A) Orientation of the hTAF[II]250-DBD is the same as that of Fig. 2. Numerous clustered lysine and arginine residues result in an extended basic surface. (B) Reverse side of the double bromodomain relative to (A) displaying the acidic stripe present running across the top of the molecule. (C) Putative binding surface of the double bromodomain viewed from the bottom surface of (A). Two deep pits (labeled) at the center of each four-helix bundle are readily apparent and are separated by about 25 Å.

Figure 4.
Fig. 4. Simplified model for assembly of transcription complexes on chromatin-bound templates. First, recruitment of a HAT-containing coactivator complex via interactions with an upstream DNA binding protein occurs. After recruitment, the coactivator HAT activity might acetylate the NH[2]-terminal histone tails (light blue tails) of nearby nucleosomes (upper). Acetylated histone tails positioned at an appropriate distance from the start site of a gene might then help to recruit TFIID by interactions with the TAF[II]250 bromodomains. Nonspecific interactions between the TAF[II]250 bromodomains and the promoter DNA as well as other TAF-DNA interactions could further increase affinity of TFIID for the core promoter. The bromodomain-mediated increase in affinity for the acetylated histones near the core promoter would provide a linkage between histone acetylation and transcriptional activation by enhanced preinitiation complex formation. Such a model would not preclude other activation pathways.

The above figures are reprinted by permission from the AAAs: Science (2000, 288, 1422-1425) copyright 2000.

Figures were selected by an automated process.