Recycling of eIF2:GDP

Stable Identifier
R-HSA-72731
Type
Pathway
Species
Homo sapiens
Compartment
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The active eIF2:GTP complex may be formed by direct binding of GTP to free eIF2 or by GDP-GTP exchange on the eIF2:GDP:eIF2B complex. The eIF2:GDP complex binds eIF2B forming an eIF2:GDP:eIF2B intermediate complex. eIF2B is a guanine nucleotide releasing factor required to cause GDP release so that a new GTP molecule can bind and activate eIF2. Phosphorylated eIF2:GDP sequesters all eIF2B as an inactive complex, and thus, reuse of eIF2 is inhibited as a consequence of the tight bond it forms with eIF2B, which prevents nucleotide exchange. Therefore, in the absence of free eIF2B, excess eIF2 remains in its inactive GDP-bound form and protein synthesis slows dramatically.

Literature References
PubMed ID Title Journal Year
7063012 Phosphorylation inhibits guanine nucleotide exchange on eukaryotic initiation factor 2.

Clemens, MJ, Pain, VM, Wong, ST, Henshaw, EC

Nature 1982
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Orthologous Events