EIF-W2 protein domain

Last updated
W2
PDB 1paq EBI.jpg
crystal structure of the catalytic fragment of eukaryotic initiation factor 2b epsilon
Identifiers
SymbolW2
Pfam PF02020
Pfam clan CL0020
InterPro IPR003307
SCOP2 1paq / SCOPe / SUPFAM

In molecular biology, the protein domain eIF4-gamma/eIF5/eIF2-epsilon is a family of evolutionarily related proteins. This domain is found at the C-terminus of several translation Initiation factors. [1] It was first detected at the very C-termini of the yeast protein GCD6, eIF-2B epsilon, and two other eukaryotic translation initiation factors, eIF-4 gamma and eIF-5 and it may be involved in the interaction of eIF-2B, eIF-4 gamma, and eIF-5 with eIF-2. [1]

Contents

Function

In molecular biology, the eIF-W2 domain functions as the binding site for Mnk eIF4E kinase, [2] an enzyme that phosphorylates eukaryotic initiation factor 4E (eIF4E). For eIF2B-epsilon, the W2 C-terminal domain functions in guanine nucleotide exchange on eIF2. For eIF5, the W2 domain functions in mediating the multifactor complex (MFC) formation with eIF1, eIF2-GTP, eIF3 and Met-tRNAiMet. The eIF5 W2 C-terminal domain and the adjacent N-terminal linker region is responsible for the GDI activity against eIF2-GDP. [3]

Domain Structure

The W2 domain has a globular fold and is exclusively composed out of alpha-helices. [4] [5] [6] The structure can be divided into a structural C-terminal core onto which the two N-terminal helices are attached. The core contains two aromatic/acidic residue-rich regions (AA boxes), which are important for mediating protein-protein interactions.

This entry covers the entire W2 domain, which is part of the TPR clan.

Translation

Translation initiation is a well regulated and highly coordinated cellular process in eukaryotes, in which at least 11 eukaryotic initiation factors (eIFs) are included. [7] These factors come together to form the pre-initiation complex.

Eukaryotic initiation factors

The W2 domain (two invariant tryptophans) is a region of approximately 165 amino acids which is found in the C-terminus of the following eukaryotic initiation factors(eIFs):

Examples

Genes encoding proteins containing this domain include AAG1, BZW1, BZW2, EIF2B5, EIF4G1, EIF4G2, EIF4G3, and EIF5.

Related Research Articles

EIF4G2

Eukaryotic translation initiation factor 4 gamma 2 is a protein that in humans is encoded by the EIF4G2 gene.

Eukaryotic translation initiation factor 4 gamma 1

Eukaryotic translation initiation factor 4 gamma 1 is a protein that in humans is encoded by the EIF4G1 gene.

EIF2S1 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the EIF2S1 gene.

EIF2B5 Protein-coding gene in humans

Translation initiation factor eIF-2B subunit epsilon is a protein that in humans is encoded by the EIF2B5 gene.

EIF2B2 Protein-coding gene in the species Homo sapiens

Translation initiation factor eIF-2B subunit beta is a protein that in humans is encoded by the EIF2B2 gene.

EIF2AK3 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 2-alpha kinase 3, also known as protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), is an enzyme that in humans is encoded by the EIF2AK3 gene.

EIF2S2

Eukaryotic translation initiation factor 2 subunit 2 (eIF2β) is a protein that in humans is encoded by the EIF2S2 gene.

EIF2B1

Translation initiation factor eIF-2B subunit alpha is a protein that in humans is encoded by the EIF2B1 gene.

EIF2B4 Protein-coding gene in the species Homo sapiens

Translation initiation factor eIF-2B subunit delta is a protein that in humans is encoded by the EIF2B4 gene.

EIF2B3 Protein-coding gene in the species Homo sapiens

Translation initiation factor eIF-2B subunit gamma is a protein that in humans is encoded by the EIF2B3 gene.

EIF4G3 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 4 gamma 3 is a protein that in humans is encoded by the EIF4G3 gene. The gene encodes a protein that functions in translation by aiding the assembly of the ribosome onto the messenger RNA template. Confusingly, this protein is usually referred to as eIF4GII, as although EIF4G3 is the third gene that is similar to eukaryotic translation initiation factor 4 gamma, the second isoform EIF4G2 is not an active translation initiation factor.

EIF2S3 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 2 subunit 3 (eIF2γ) is a protein that in humans is encoded by the EIF2S3 gene.

EIF4A1 Protein coding gene in Humans

Eukaryotic initiation factor 4A-I is a 46 kDa cytosolic protein that, in humans, is encoded by the EIF4A1 gene, which is located on chromosome 17. It is the most prevalent member of the eIF4A family of ATP-dependant RNA helicases, and plays a critical role in the initiation of cap-dependent eukaryotic protein translation as a component of the eIF4F translation initiation complex. eIF4A1 unwinds the secondary structure of RNA within the 5'-UTR of mRNA, a critical step necessary for the recruitment of the 43S preinitiation complex, and thus the translation of protein in eukaryotes. It was first characterized in 1982 by Grifo, et al., who purified it from rabbit reticulocyte lysate.

EIF2AK1 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 2-alpha kinase 1 is an enzyme that in humans is encoded by the EIF2AK1 gene.

EIF3B Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 3 subunit B (eIF3b) is a protein that in humans is encoded by the EIF3B gene.

Basic leucine zipper and W2 domain-containing protein 2 Protein-coding gene in the species Homo sapiens

Basic Leucine Zipper and W2 Domain-Containing Protein 2 is a protein that is encoded by the BZW2 gene. It is a eukaryotic translation factor found in species up to bacteria. In animals, it is localized in the cytoplasm and expressed ubiquitously throughout the body. The heart, placenta, skeletal muscle, and hippocampus show higher expression. In various cancers, upregulation tends to lead to higher severity and mortality. It has been found to interact with SARS-CoV-2.

Eukaryotic translation initiation factor 4 G (eIF4G) is a protein involved in eukaryotic translation initiation and is a component of the eIF4F cap-binding complex. Orthologs of eIF4G have been studied in multiple species, including humans, yeast, and wheat. However, eIF4G is exclusively found in domain Eukarya, and not in domains Bacteria or Archaea, which do not have capped mRNA. As such, eIF4G structure and function may vary between species, although the human EIF4G1 has been the focus of extensive studies.

eIF2B is a protein complex found in eukaryotes. It is the guanine nucleotide exchange factor for the eukaryotic initiation factor 2 and therefore converts the inactive eIF2-GDP to the active eIF2-GTP. This activation is hindered by phosphorylation of the alpha subunit of eIF2, which leads to a stable eIF2α-P-GDP-eIF2B complex and therefore inhibits translation initiation.

Eukaryotic Initiation Factor 2 (eIF2) is a eukaryotic initiation factor. It is required for most forms of eukaryotic translation initiation. eIF2 mediates the binding of tRNAiMet to the ribosome in a GTP-dependent manner. eIF2 is a heterotrimer consisting of an alpha, a beta, and a gamma subunit.

The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that function to unwind double-stranded RNA.

References

  1. 1 2 Koonin EV (1995). "Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs". Protein Sci. 4 (8): 1608–1617. doi:10.1002/pro.5560040819. PMC   2143190 . PMID   8520487.
  2. ↑ Singh CR, Watanabe R, Zhou D, Jennings MD, Fukao A, Lee B, et al. (2011). "Mechanisms of translational regulation by a human eIF5-mimic protein". Nucleic Acids Res. 39 (19): 8314–28. doi:10.1093/nar/gkr339. PMC   3201852 . PMID   21745818.
  3. ↑ Fukunaga R, Hunter T (1997). "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates". EMBO J. 16 (8): 1921–33. doi:10.1093/emboj/16.8.1921. PMC   1169795 . PMID   9155018.
  4. ↑ Boesen T, Mohammad SS, Pavitt GD, Andersen GR (March 2004). "Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue". J. Biol. Chem. 279 (11): 10584–92. doi: 10.1074/jbc.M311055200 . PMID   14681227.
  5. ↑ Wei Z, Xue Y, Xu H, Gong W (May 2006). "Crystal structure of the C-terminal domain of S.cerevisiae eIF5". J. Mol. Biol. 359 (1): 1–9. doi:10.1016/j.jmb.2006.03.037. PMID   16616930.
  6. ↑ Bieniossek C, Schütz P, Bumann M, Limacher A, Uson I, Baumann U (July 2006). "The crystal structure of the carboxy-terminal domain of human translation initiation factor eIF5". J. Mol. Biol. 360 (2): 457–65. doi:10.1016/j.jmb.2006.05.021. PMID   16781736.
  7. ↑ Koonin EV (August 1995). "Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs". Protein Sci. 4 (8): 1608–17. doi:10.1002/pro.5560040819. PMC   2143190 . PMID   8520487.
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