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Crystal structure of the eukaryotic translation initiation factor 2A from Schizosaccharomyces pombe.

Kashiwagi K, Ito T, Yokoyama S - J. Struct. Funct. Genomics (2014)

Bottom Line: The structure adopts a novel nine-bladed β-propeller fold.In contrast to the usual β-propeller proteins, the central channel of the molecule has the narrower opening on the bottom of the protein and the wider opening on the top.Highly conserved residues are concentrated in the positively-charged top face, suggesting the importance of this face for interactions with nucleic acids or other initiation factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

ABSTRACT
The eukaryotic translation initiation factor 2A (eIF2A) was identified as a factor that stimulates the binding of methionylated initiator tRNA (Met-tRNA i (Met) ) to the 40S ribosomal subunit, but its physiological role remains poorly defined. Recently, eIF2A was shown to be involved in unconventional translation initiation from CUG codons and in viral protein synthesis under stress conditions where eIF2 is inactivated. We determined the crystal structure of the WD-repeat domain of Schizosaccharomyces pombe eIF2A at 2.5 Å resolution. The structure adopts a novel nine-bladed β-propeller fold. In contrast to the usual β-propeller proteins, the central channel of the molecule has the narrower opening on the bottom of the protein and the wider opening on the top. Highly conserved residues are concentrated in the positively-charged top face, suggesting the importance of this face for interactions with nucleic acids or other initiation factors.

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Related in: MedlinePlus

Conservation and electrostatic potential of the molecular surface of eIF2A-WD. a–c Three views of eIF2A-WD. d–f Conservation plot of the surface-exposed residues. Highly conserved and variable residues are colored magenta and cyan, respectively. g–i The electrostatic surface potential of eIF2A-WD, in which red and blue colors respectively represent negative and positive potentials of ±5 kT
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Fig2: Conservation and electrostatic potential of the molecular surface of eIF2A-WD. a–c Three views of eIF2A-WD. d–f Conservation plot of the surface-exposed residues. Highly conserved and variable residues are colored magenta and cyan, respectively. g–i The electrostatic surface potential of eIF2A-WD, in which red and blue colors respectively represent negative and positive potentials of ±5 kT

Mentions: Whereas the AB and CD loops at the bottom face have similar lengths and structures, the BC loops at the top face have various lengths and directions (Fig. 1d). A phylogenetic analysis revealed that the surface residues on the top face of eIF2A-WD, including these loops, are highly conserved, in contrast to the abundance of non-conserved residues on the bottom face (Figs. 2d–f). Especially, the residues at the top faces of blades 6–9 showed strong conservation. This highly conserved top face is positively charged (Fig. 2g), and the most positively-charged regions are the grooves between blades 3–4 and between blades 6–7. In addition, like the top face, the exterior face of blade 5 is highly conserved and positively charged (Fig. 2h). In many cases, the β-propeller domain plays an important role as a platform for protein–protein interactions. The existence of flexible long loops and the high surface-residue conservation at the top face of eIF2A-WD strongly suggest that this face plays such a platform-like role. Since eIF2A is implicated in interactions with nucleic acids, such as rRNA, tRNA, or IRES, the positive charges of the top face and the neighboring exterior face would be favorable for such interactions.Fig. 2


Crystal structure of the eukaryotic translation initiation factor 2A from Schizosaccharomyces pombe.

Kashiwagi K, Ito T, Yokoyama S - J. Struct. Funct. Genomics (2014)

Conservation and electrostatic potential of the molecular surface of eIF2A-WD. a–c Three views of eIF2A-WD. d–f Conservation plot of the surface-exposed residues. Highly conserved and variable residues are colored magenta and cyan, respectively. g–i The electrostatic surface potential of eIF2A-WD, in which red and blue colors respectively represent negative and positive potentials of ±5 kT
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4125824&req=5

Fig2: Conservation and electrostatic potential of the molecular surface of eIF2A-WD. a–c Three views of eIF2A-WD. d–f Conservation plot of the surface-exposed residues. Highly conserved and variable residues are colored magenta and cyan, respectively. g–i The electrostatic surface potential of eIF2A-WD, in which red and blue colors respectively represent negative and positive potentials of ±5 kT
Mentions: Whereas the AB and CD loops at the bottom face have similar lengths and structures, the BC loops at the top face have various lengths and directions (Fig. 1d). A phylogenetic analysis revealed that the surface residues on the top face of eIF2A-WD, including these loops, are highly conserved, in contrast to the abundance of non-conserved residues on the bottom face (Figs. 2d–f). Especially, the residues at the top faces of blades 6–9 showed strong conservation. This highly conserved top face is positively charged (Fig. 2g), and the most positively-charged regions are the grooves between blades 3–4 and between blades 6–7. In addition, like the top face, the exterior face of blade 5 is highly conserved and positively charged (Fig. 2h). In many cases, the β-propeller domain plays an important role as a platform for protein–protein interactions. The existence of flexible long loops and the high surface-residue conservation at the top face of eIF2A-WD strongly suggest that this face plays such a platform-like role. Since eIF2A is implicated in interactions with nucleic acids, such as rRNA, tRNA, or IRES, the positive charges of the top face and the neighboring exterior face would be favorable for such interactions.Fig. 2

Bottom Line: The structure adopts a novel nine-bladed β-propeller fold.In contrast to the usual β-propeller proteins, the central channel of the molecule has the narrower opening on the bottom of the protein and the wider opening on the top.Highly conserved residues are concentrated in the positively-charged top face, suggesting the importance of this face for interactions with nucleic acids or other initiation factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

ABSTRACT
The eukaryotic translation initiation factor 2A (eIF2A) was identified as a factor that stimulates the binding of methionylated initiator tRNA (Met-tRNA i (Met) ) to the 40S ribosomal subunit, but its physiological role remains poorly defined. Recently, eIF2A was shown to be involved in unconventional translation initiation from CUG codons and in viral protein synthesis under stress conditions where eIF2 is inactivated. We determined the crystal structure of the WD-repeat domain of Schizosaccharomyces pombe eIF2A at 2.5 Å resolution. The structure adopts a novel nine-bladed β-propeller fold. In contrast to the usual β-propeller proteins, the central channel of the molecule has the narrower opening on the bottom of the protein and the wider opening on the top. Highly conserved residues are concentrated in the positively-charged top face, suggesting the importance of this face for interactions with nucleic acids or other initiation factors.

Show MeSH
Related in: MedlinePlus