Question

The phosphorylation of eIF2 directly inhibits translation initiation by:

A. Preventing interactions with the tRNA
B. enhancing the binding of eIF2-GDP for the initiator tRNA.
C. targeting the protein for degradation.
D. sequestering the available eIF2B protein.

Answer 1

Phosphorylation of eIF2 inhibits translation initiation by sequestering eIF2B protein and preventing the formation of the initiation complex, necessary for the association of the small (40S) ribosomal subunit, initiator tRNA, and mRNA, which is critical in the process of translation initiation.

Step-by-step explanation:

The phosphorylation of eIF2 directly inhibits translation initiation by sequestering the available eIF2B protein. This happens because phosphorylated eIF2 undergoes a conformational change that prevents its interaction with GTP, which is essential for the formation of the initiation complex. Without the ability to form this complex, the small (40S) ribosomal subunit and the methionine initiator tRNA cannot properly associate with the mRNA to be translated, thus impeding translation initiation.

Further, in the context of neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's, an increase in phosphorylation levels of eIF-2 could lead to the inhibition of protein synthesis, which may contribute to the pathology of these diseases by affecting the synthesis of crucial proteins for neuronal function.