Journal:Acta Cryst D:S2059798319002304

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In this work, the structure of aIF2gamma from Sulfolobus solfataricus obtained in the absence of magnesium ions clarified two important problems of translation initiation: (i) magnesium ion is necessary for the formation of the active GTP-bound form of the gamma subunit. In its absence, switch 1 cannot take the form of an alpha helix and shield the phosphate moiety of GTP from the solvent and (ii) a structural motif capable of accepting two different conformations and containing strongly conserved amino acid residues was found in the domain II of the aIF2gamma and called switch 3. This switch possibly allows the codon-anticodon recognition signal to be transmitted to switch 1, causing the necessary rearrangement of this switch, which leads to the start of GTP hydrolysis and dissociation aIF2 from IC.
In this work, the structure of aIF2gamma from Sulfolobus solfataricus obtained in the absence of magnesium ions clarified two important problems of translation initiation: (i) magnesium ion is necessary for the formation of the active GTP-bound form of the gamma subunit. In its absence, switch 1 cannot take the form of an alpha helix and shield the phosphate moiety of GTP from the solvent and (ii) a structural motif capable of accepting two different conformations and containing strongly conserved amino acid residues was found in the domain II of the aIF2gamma and called switch 3. This switch possibly allows the codon-anticodon recognition signal to be transmitted to switch 1, causing the necessary rearrangement of this switch, which leads to the start of GTP hydrolysis and dissociation aIF2 from IC.
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Two views of SsoIF2gamma-GDPCP molecules in unit cell of the crystal. Molecules are colored: A-cyan, B-magenta, C-green, D-yellow and E-red.
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Two views of SsoIF2gamma-GDPCP molecules in unit cell of the crystal ([[6h6k]]). Molecules are colored: A-cyan, B-magenta, C-green, D-yellow and E-red.
*a) <scene name='81/813414/Cv/3'>Two-fold non-crystallographic symmetry axis, pairwise connecting molecules A-B and C-D, is parallel to the plane of the figure</scene>.
*a) <scene name='81/813414/Cv/3'>Two-fold non-crystallographic symmetry axis, pairwise connecting molecules A-B and C-D, is parallel to the plane of the figure</scene>.
*b) <scene name='81/813414/Cv/4'>Molecules form a structure resembling an armchair</scene>.
*b) <scene name='81/813414/Cv/4'>Molecules form a structure resembling an armchair</scene>.
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Closed and open conformations of switch 3 in SsoIF2γ. <scene name='81/813414/Cv/7'>Superposition of domains II of molecule A (closed conformation, shown in blue) and molecule E (open conformation, shown in orange)</scene> of the presented structure. The γL1 loop of molecule A is shown in cyan and that of molecule E in yellow. The new β-strand 310–312 (shown in green) formed by switch 3 in the closed conformation is antiparallel to strand 258–260 (marked in magenta).
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Closed and open conformations of switch 3 in SsoIF2γ. <scene name='81/813414/Cv/7'>Superposition of domains II of molecule A (closed conformation, shown in blue) and molecule E (open conformation, shown in orange)</scene> of the presented structure ([[6h6k]]). The γL1 loop of molecule A is shown in cyan and that of molecule E in yellow. The new β-strand 310–312 (shown in green) formed by switch 3 in the closed conformation is antiparallel to strand 258–260 (marked in magenta).
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Superposition of the nucleotide-binding pockets of the molecule E (blue) of the presented structure and the SsoIF2gamma-GDPCP complex obtained in the presence of Mg2+ (PDB code [[4rjl]], orange).
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<scene name='81/813414/Cv/10'>Superposition of the nucleotide-binding pockets</scene> of the molecule E (blue) of the presented structure and the SsoIF2gamma-GDPCP complex obtained in the presence of Mg2+ (PDB code [[4rjl]], orange). The nucleotide, residues Thr23, Ser35, Thr46 and the hydrogen bonds formed by them are shown only for molecule E. Side chains of Ser35 and Thr46 approach, distorting the portion of switch 1 located between them.
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'''PDB references:''' The structure of the FKR mutant of the archaeal translation initiation factor 2 gamma subunit in complex with GDPCP, obtained in the absence of magnesium salts in the crystallization solution [[6h6k]]; Gamma subunit of the translation initiation factor 2 from ''Sulfolobus solfataricus'' in complex with GDP and formate ion [[6i5m]].
<b>References</b><br>
<b>References</b><br>

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