PDBsum entry: 1paq

Translation

PDB id: 1paq

Contents

Protein chain

161 a.a. *

Waters ×90

* Residue conservation analysis

PDB id:

1paq

Name:

Translation

Title:

Crystal structure of the catalytic fragment of eukaryotic initiation factor 2b epsilon

Structure:

Translation initiation factor eif-2b epsilon subunit. Chain: a. Fragment: catalytic domain, residues (524-712). Synonym: eif-2b gdp-gtp exchange factor, guanine nucleotide exchange factor subunit gcd6, gcd complex subunit gcd6. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: gcd6 or tif225 or ydr211w or yd8142.12 or yd8142b.03. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å R-factor: 0.243 R-free: 0.272

Authors:

T.Boesen,G.R.Andersen,G.D.Pavitt

Key ref:

T.Boesen et al. (2004). Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue. J Biol Chem, 279, 10584-10592. PubMed id: 14681227 DOI: 10.1074/jbc.M311055200

Date:

14-May-03 Release date: 10-Feb-04

Protein chain

P32501  (EI2BE_YEAST) -  Translation initiation factor eIF-2B subunit epsilon

Seq: 712 a.a.

Struc: 161 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: RNA metabolic process (1 term)
• Biochemical function: binding (2 terms)

DOI no: 10.1074/jbc.M311055200

J Biol Chem 279:10584-10592 (2004)

PubMed id: 14681227

Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue.

T.Boesen, S.S.Mohammad, G.D.Pavitt, G.R.Andersen.

ABSTRACT

Eukaryotic initiation factor (eIF) 2B catalyzes the nucleotide activation of eIF2 to its active GTP-bound state. The exchange activity has been mapped to the C terminus of the eIF2Bepsilon subunit. We have determined the crystal structure of residues 544-704 from yeast eIF2Bepsilon at 2.3-A resolution, and this fragment is an all-helical protein built around the conserved aromatic acidic (AA) boxes also found in eIF4G and eIF5. The eight helices are organized in a manner similar to HEAT repeats. The molecule is highly asymmetric with respect to surface charge and conservation. One area in the N terminus is proposed to be directly involved in catalysis. In agreement with this hypothesis, mutation of glutamate 569 is shown to be lethal. An acidic belt and a second area in the C terminus containing residues from the AA boxes are important for binding to eIF2. Two mutations causing the fatal human genetic disease leukoencephalopathy with vanishing white matter are buried and appear to disrupt the structural integrity of the catalytic domain rather than interfering directly with catalysis or binding of eIF2.

Selected figure(s)

Figure 1.
FIG. 1. Electron density of helix VIII from the experimental map obtained from MAD phases after density modification. Helix VIII of one molecule of eIF2B C (gray carbons) packs with a symmetry related helix VIII (gold carbons). The contacts are dominated by the stacking of Trp699 with the corresponding residue of the neighbor molecule. The electron density map is contoured at 1.7 and plotted with the map_cover option in the program O (18) using a radius of 1 Å.

Figure 4.
FIG. 4. Stereoview of superimposition of C traces of eIF2B C (gray), eight helices of the human 80-kDa subunit of the cap binding complex (red), and six helices of the middle domain of human eIF4GII (blue). The C-terminal six helices of eIF2B C constitute a structural core in common with the 80-kDa subunit of the cap binding complex (27) and eIF4GII (28). Helix numbering is shown in Roman numerals.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 10584-10592) copyright 2004.

Figures were selected by an automated process.