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Terri Goss-Kinzy, PhD
Publications
Click Here for PubMed Link to Publications
Lab Staff
DNA Lab Staff
Images
X-ray Crystal structure of yeast Translation Elongation Factor 1A (gold) with the nucleotide exchange factor 1Bα (silver) Research InterestsResearch Interests The goal of the work in our laboratory is to understand the structural and functional basis of G-protein regulation and post-transcriptional mechanisms that regulate gene expression. The components of the Translation Elongation apparatus in yeast, from soluble protein factors to the ribosome, allow an integrated approach to these questions. These components are targets for antibiotics and antifungals, mutant forms and inappropriate expression of these proteins are found in several human carcinomas, and mutations in several components affect the accuracy and efficiency of protein synthesis and viral replication. We are applying complementary genetic, molecular, biochemical and structural techniques to dissect the mechanism of events occurring during protein synthesis. These include probing the physical and functional interaction of Elongations Factors (eEFs) with other factors that regulate gene expression, and the interaction between the G-proteins in elongation with the ribosome. The eEF1 protein complex is prototypical of all G-proteins, such as the oncogene Ras, and as such is regulated by a classic "GTPase" switch mechanism. The GTP-dependent activity of eEF1A is to deliver aminoacyl-tRNA to the ribosome and sense the accuracy of this process. The guanine nucleotide exchange factor (GEF) eEF1Balpha is essential in yeast and responsible for catalyzing the exchange of GDP for GTP to maintain the pool of active protein. Using a genetic system devoid of the eEF1Balpha protein allows us to manipulate eEF1A without its GEF to understand the regulation of G-protein activity and mutant forms of eEF1Balpha allow us to dissect the mechanism of guanine nucleotide exchange in vitro and the consequences of changes in this protein's activity in vivo. Using this approach we have isolated a novel prion-like element in yeast. Lastly, the eEF1Bgamma subunit affects the sensitivity of the cell to oxidative stress. Current work is addressing the implications of this finding in post-transcriptional control using a proteomics approach. Integrating an analysis of the two other factors involved in elongation, the translocase for the growing peptide chain eEF2 and the fungal specific factor eEF3 allows us to fully dissect the elongation cycle and to better understand their potential as drug targets. We are currently performing X-ray crystallographic studies of the eEF1 complex, the eEF1A-actin interaction, and the other elongation factors eEF2 and eEF3. Additionally, we are part of an international consortium with groups from Denmark and U. Penn. using a combined genetic, biophysical and structural approach to the study of the yeast ribosome. |
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