Section on Nutrient Control of Gene Expression

Head: Alan G. Hinnebusch

We are studying the mechanism and regulation of protein synthesis, focusing on GTPases and protein kinases that control this fundamental cellular process. We use molecular-genetic and biochemical studies to dissect the structure-function properties of the translation initiation factor eIF2, a GTPase that binds methionyl-tRNA to the ribosome. We are also studying how phosphorylation regulates eIF2 function. Focusing on the kinases that phosphorylate eIF2alpha, we recently showed that a common dimer configuration is required for activation of the antiviral kinase PKR, the ER (endoplasmic reticulum) stress–responsive kinase PERK, and the endogenous yeast kinase GCN2. In addition, we are studying viral regulation of PKR by poxvirus inhibitors of the kinase. The translation factor eIF5B is a second GTPase that catalyzes ribosomal subunit joining in the final step of translation initiation. Our recent mutational and suppressor analyses, combined with biochemical studies, provide new insights into the structure-function properties of eIF5B—a universally conserved factor—and define the critical role of GTP hydrolysis by eIF5B in releasing both eIF5B and the factor eIF1A from the ribosome following subunit joining.

Resources

• Employee Listing
• E-Mail the Lab: alanh@box-a.nih.gov
• SNCGE Home Page