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SUI2 (YJR007W) encodes the alpha subunit of the heterotrimeric eIF2 complex
(eIF2alpha/Sui2, eIF2beta/Sui3, eIF2gamma/Gcd11); eIF2 binds GTP and initiator
Met-tRNAi to form the ternary complex that delivers initiator tRNA to the 40S
ribosome and assembles the 43S/48S preinitiation complex.
"SUI2 in *Saccharomyces cerevisiae* (S288c; ORF YJR007W) encodes the **α subunit of eukaryotic translation initiation factor 2 (eIF2α)**, a core component of the heterotrimeric eIF2 complex (eIF2α/Sui2, eIF2β/Sui3, eIF2γ/Gcd11)"
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eIF2alpha is non-enzymatic; its primary molecular function is to contribute to
formation and function of the eIF2.GTP.Met-tRNAi ternary complex and to start-codon
selection. GTP binding/GTPase activity reside in the gamma subunit.
"SUI2 (UniProt P20459) encodes yeast eIF2α, a non-enzymatic translation initiation factor whose **primary molecular function** is to contribute to formation and function of the eIF2·GTP·Met-tRNAi ternary complex"
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After start-codon recognition eIF2 hydrolyzes GTP and leaves the ribosome in the
GDP-bound state; reactivation requires the GEF eIF2B to catalyze GDP-to-GTP exchange,
a cycle essential for continued rounds of initiation.
"After start-codon recognition, eIF2 hydrolyzes GTP and leaves the ribosome in a GDP-bound state. Reactivation requires the guanine nucleotide exchange factor **eIF2B**, which catalyzes **GDP→GTP exchange** on eIF2."
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Phosphorylation of eIF2alpha at the conserved Ser51 site by the kinase Gcn2 converts
eIF2 from an eIF2B substrate into an inhibitor of eIF2B, lowering eIF2-GTP and ternary
complex abundance and decreasing general translation initiation.
"A conserved translational-control mechanism in yeast is **phosphorylation of eIF2α at Ser51** by the kinase **Gcn2**. This single-site phosphorylation changes eIF2 from an eIF2B substrate into an **inhibitor of eIF2B**, lowering eIF2-GTP and TC abundance and thereby decreasing general translation initiation."
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In the general amino acid control (GAAC), amino acid limitation increases uncharged
tRNAs that activate Gcn2 (via Gcn1/Gcn20), triggering Ser51 phosphorylation of
eIF2alpha; this represses bulk initiation while derepressing GCN4 via uORF-mediated
reinitiation control.
"In budding yeast, amino acid limitation increases **deacylated (uncharged) tRNAs**, which activate **Gcn2** (facilitated by **Gcn1/Gcn20**), causing **Ser51 phosphorylation of eIF2α**. This reduces TC abundance and globally represses initiation, while enabling selective translation of stress-response transcripts—classically **GCN4**, whose uORF architecture makes its translation inversely related to TC availability."
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eIF2alpha comprises three domains - an N-terminal OB-fold, a central alpha-helical
domain, and a C-terminal alpha/beta domain that contacts eIF2gamma; the regulatory
Ser51 lies in a mobile loop within the OB-fold domain.
"A yeast-focused synthesis of translation mechanisms describes eIF2α as composed of **three domains**: an **N-terminal OB-fold**, a **central α-helical domain**, and a **C-terminal α/β domain** that contacts eIF2γ. The **regulatory Ser51** is located in a mobile loop within the OB-fold domain."
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eIF2alpha contributes directly to start-codon selection fidelity: its unstructured
N-terminal tail interacts with eIF1 to stabilize the open/scanning PIC and rearranges
upon AUG recognition, and residue R53 contacts rRNA helix 23 while Arg55/Arg57 contact
mRNA context near the start site.
"R53 contacts rRNA helix 23; Arg55/Arg57 contact mRNA context near the start site; unstructured N-terminal tail interacts with eIF1 in the open PIC and later with eIF5-CTD after AUG recognition"
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The yeast Sui2 phosphosite Ser52 (UniProt numbering) corresponds to the conserved
cross-species Ser51 regulatory residue used in most antibodies and studies.
"Sui2 phosphosite is adjacent to the canonical Ser51 numbering convention used in many studies/antibodies"
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Phosphorylated eIF2 binds eIF2B with ~10-fold higher affinity than unphosphorylated
eIF2 (Kd 3.5 nM vs 32.2 nM), supporting the model in which eIF2alpha-P sequesters and
inhibits the eIF2B GEF.
"phosphorylated eIF2 was reported (in the paper’s cited measurement) to have ~10-fold higher affinity for eIF2B than unphosphorylated eIF2 (Kd **3.5 nM vs 32.2 nM**), supporting the sequestration/inhibition model."
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The Gcn2-eIF2alpha Ser51 switch operates in stress responses beyond classic amino
acid starvation: a phospho-dead sui2-S51A mutant is acid-sensitive, and the pathway
limits initiation under severe iron deficiency.
"a phosphorylation-defective **sui2-S51A** mutant is acid-sensitive, implicating the eIF2α phosphorylation switch in adaptation."