What does eIF2B do?

eIF2B is a multisubunit protein that is critical for protein synthesis initiation and its control. It is a guanine nucleotide exchange factor (GEF) for its GTP-binding protein partner eIF2. eIF2 binds initiator tRNA to ribosomes and promotes mRNA AUG codon recognition.

What is the purpose of eIF 2 phosphorylation and how does it effect protein synthesis?

A central mechanism for translational control involves phosphorylation of the α subunit of eukaryotic initiation factor (eIF) 2 (eIF2α~P),3 which represses the initiation phase of protein synthesis, allowing cells to conserve resources while a new gene expression program is adopted to prevent stress damage.

Is GEF a Gtpase?

Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP).

How is eIF2 regulated?

eIF2 activation is highly regulated. In response to a wide range of signals, multiple protein kinases phosphorylate a single serine, historically known as Ser51, within the eIF2α subunit. This inhibits the GEF activity of eIF2B forming a tight eIF2αP/eIF2B inhibitory complex3,9,10.

What is the purpose of eIF2 binding to GTP?

eIF2 plays a central role in the maintenance of what is generally considered a rate-limiting step in mRNA translation. In this step, eIF2 binds GTP and Met-tRNAi and transfers Met-tRNAi to the 40S ribosomal subunit. At the end of the initiation process, GTP bound to eIF2 is hydrolyzed to GDP and the eIF2.

What is Gap vs GEF?

In general, GEFs turn on signaling by catalyzing the exchange from G-protein-bound GDP to GTP, whereas GAPs terminate signaling by inducing GTP hydrolysis. GEFs and GAPs are multidomain proteins that are regulated by extracellular signals and localized cues that control cellular events in time and space.

What does eIF4E bind to?

eIF4E is the cap-binding protein which, in synergy with proteins such as the helicase eIF4A and the scaffolding protein eIF4G, binds to mRNA, allowing the recruitment of ribosomes and translation initiation.

What is the role of eIF4E in Polysomal translation?

Eukaryotic initiation factor eIF4E plays a pivotal role in translation initiation. As a component of the ternary eIF4F complex, eIF4E interacts with the mRNA cap structure to facilitate recruitment of the 40S ribosomal subunit onto mRNA.