PDBsum entry 4zem

Translation

PDB id: 4zem

Contents

Protein chains

328 a.a.

298 a.a.

Waters ×60

PDB id:

4zem

Name:

Translation

Title:

Crystal structure of eif2b beta from chaetomium thermophilum

Structure:

Translation initiation factor eif2b-like protein, translation initiation factor eif2b-like protein. Chain: a, b. Engineered: yes

Source:

Chaetomium thermophilum. Organism_taxid: 209285. Gene: ctht_0063470. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.55Å R-factor: 0.177 R-free: 0.204

Authors:

B.Kuhle,R.Ficner

Key ref:

B.Kuhle et al. (2015). Architecture of the eIF2B regulatory subcomplex and its implications for the regulation of guanine nucleotide exchange on eIF2. Nucleic Acids Res, 43, 9994. PubMed id: 26384431 DOI: 10.1093/nar/gkv930

Date:

20-Apr-15 Release date: 30-Sep-15

Protein chain

G0SEE6  (G0SEE6_CHATD) -  Translation initiation factor eIF2b-like protein from Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)

Seq: 388 a.a.

Struc: 328 a.a.*

Protein chain

G0SEE6  (G0SEE6_CHATD) -  Translation initiation factor eIF2b-like protein from Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)

Seq: 388 a.a.

Struc: 298 a.a.*

* PDB and UniProt seqs differ at 27 residue positions (black crosses)

DOI no: 10.1093/nar/gkv930

Nucleic Acids Res 43:9994 (2015)

PubMed id: 26384431

Architecture of the eIF2B regulatory subcomplex and its implications for the regulation of guanine nucleotide exchange on eIF2.

B.Kuhle, N.K.Eulig, R.Ficner.

ABSTRACT

Eukaryal translation initiation factor 2B (eIF2B) acts as guanine nucleotide exchange factor (GEF) for eIF2 and forms a central target for pathways regulating global protein synthesis. eIF2B consists of five non-identical subunits (α-ϵ), which assemble into a catalytic subcomplex (γ, ϵ) responsible for the GEF activity, and a regulatory subcomplex (α, β, δ) which regulates the GEF activity under stress conditions. Here, we provide new structural and functional insight into the regulatory subcomplex of eIF2B (eIF2B(RSC)). We report the crystal structures of eIF2Bβ and eIF2Bδ from Chaetomium thermophilum as well as the crystal structure of their tetrameric eIF2B(βδ)2 complex. Combined with mutational and biochemical data, we show that eIF2B(RSC) exists as a hexamer in solution, consisting of two eIF2Bβδ heterodimers and one eIF2Bα2 homodimer, which is homologous to homohexameric ribose 1,5-bisphosphate isomerases. This homology is further substantiated by the finding that eIF2Bα specifically binds AMP and GMP as ligands. Based on our data, we propose a model for eIF2B(RSC) and its interactions with eIF2 that is consistent with previous biochemical and genetic data and provides a framework to better understand eIF2B function, the molecular basis for Gcn(-), Gcd(-) and VWM/CACH mutations and the evolutionary history of the eIF2B complex.