Time: 15:00
Location: ENG B16

Speaker         :
Cory Dunn, Ph.D., University Researcher (Docent) Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki and Visiting Scholar, College of Sciences, Koç University

Title                : Tail anchor targeting to organelles

Date                : October 19, 2018 Friday
Time               : 15:00   
Cookie & Tea: 14:45 ENG B16 
Place               : ENG B16

Abstract         :   Proteins localized to mitochondria by a carboxyl-terminal tail anchor (TA) play important roles in apoptosis, mitochondrial dynamics, and mitochondrial protein import. In order to reveal structural characteristics of TAs that may be important for mitochondrial targeting, we focused our attention upon the TA of the Saccharomyces cerevisiae Fis1 protein. We generated a library of Fis1p TA variants fused to the transcription factor Gal4p, and by selecting for mutations within the TA that permit Gal4p to translocate to the nucleus and activate transcription, we were able to enrich for TA variants within our mutant pool which led to decreased membrane insertion. Next-generation sequencing allowed quantification of each TA variant in our mutant library before and after selection, and high-throughput results were confirmed by microscopy-based and functional analysis of individual, reconstructed Fis1p TA mutants. Most prominently, while charged residues within the hydrophobic core of the Fis1p TA were also able to perturb membrane insertion, we found that positively charged residues were much more acceptable at several positions within the Fis1p TA than negatively charged residues. These results provide strong, in vivo evidence that lysine and arginine can “snorkel,” or partition the non-polar portion of their side chains into the hydrophobic region of the lipid bilayer while placing the terminal charge near the polar interface of the membrane.


TAs are not only used by cells to target proteins to mitochondria, but also to direct proteins to other organelles. Moreover, prokaryotes can provide new genetic information to eukaryotes by horizontal gene transfer (HGT), and such transfers are likely to have been particularly consequential during the early evolution of eukaryotes. We will discuss our recent results regarding the specific targeting of bacterial TAs to organelles in yeast and human cells, and we will explain how we are capitalizing upon our findings to understand peroxisomal assembly. Our findings highlight the ease with which bacteria-derived sequences might target to distinct organelles in eukaryotic cells following HGT, and we discuss the importance of flexible recognition of organelle targeting information during and after eukaryogenesis.


Bio         : After completing his Ph.D. studies at Johns Hopkins School of Medicine and his post-doctoral work at Columbia University, Dr. Dunn became a founding member of Koç University’s Molecular Biology and Genetics Department. He has received the EMBO Installation Grant, the ERC Starting Grant, the Turkish Academy of Sciences Outstanding Young Scientist Award, the Science Academy Young Scientist Award, and the College of Science’s Outstanding Faculty Award."