Scientists have uncovered key new information towards understanding the crucial first step in protein synthesis, the process by which the genetic code, harbored within DNA and copied into RNA, is translated into the production of proteins. This new information also helps to explain how viruses, such as Hepatitis C, are able to highjack protein synthesis machinery in humans for their own purposes.

Biochemist Jennifer Doudna and biophysicist Eva Nogales, both of whom hold joint appointments with the Lawrence Berkeley National Laboratory (Berkeley Lab), the University of California at Berkeley, and the Howard Hughes Medical Institute (HHMI), led a study in which cryo electron microscopy (cryo-EM) was used to create a 3-D model of the protein complex called eukaryotic translation initiation factor 3 (eIF3). The model showed that the eIF3 protein complex employs the same structural mechanics in the loading of either human or viral RNA to ribosomes, the complex machinery in living cells responsible for protein synthesis.

"This is the first insight into how the initiation mechanisms of protein synthesis work specifically for humans, and a step towards understanding at the molecular level what happens when a viral infection occurs," said Doudna, a member of Berkeley Lab's Physical Biosciences Division. "A better understanding of these mechanisms could open the door to new and improved therapies for viral infections."

Said Nogales, also a member of Berkeley Lab's Physical Biosciences Division, "Using cryo-EM, we can reconstruct images of the entire protein ensemble to study the molecular machinery behind the protein synthesis process. We now have the tools to see how the many different parts of the molecular machinery come together."

The results of this study are in the December 2, 2005 issue of the journal Science, in a paper entitled Structural Roles for Human Translation Factor eIF3 in Initiation of Protein Synthesis. Co-aut
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
2-Dec-2005

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