Initiation: the Geekview

Lest you get too comfortable, it's important to remind you that this process is horribly complex. However, if you look at the diagram below and let your eyes glaze over just a bit (which they probably will anyway), you can perceive that there are two big processes taking place:

    1. Introduction of the mRNA into the initiation complex.

    2. Introduction of the first amino acid, in the form of methionyl t-RNA, into the initiation complex.

I'm an emergency physician, which means that I like to keep things simple, so the way I've always thought about this is that translation initiation consists of a "4 side," dominated by eIF-4x molecules, which brings in the mRNA, and a "2 side," dominated by eIF2x molecules, which brings in the met-t-RNA.

Translation Initiation: the Geekview. Oh, relax. The purpose of this diagram is to illustrate how there are two "sides" to the translation initiation process: on the "4-side," eIF-4s coordinate to bring in the mRNA. On the "2-side," eIF-2 brings in the first amino acid, in the form of methionyl tRNA. Note that each time eIF-2 participates in a round of translation initiation, it must be "recharged" with GTP by the GTP-exchange factor eIF2B.

If you look closely at this figure, you'll notice that there's an extra wrinkle on the 2-side. Before eIF2 brings in met-tRNA, it must give up its spent GDP from the last round and get "recharged" with GTP. This exchange is catalyzed by the GTP-exchange factor eIF2B.

Now, it just so happens that the alpha subunit of eIF-2 can be phosphorylated at serine 51, yielding eIF-2α(P), which inhibits the GTP-GDP exchange on eIF-2 by eIF2B. And when that happens, translation initiation stops.

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