Featuring...Elke Deuerling

Abstract

Elke Deuerling grew up in Franconia, an historic duchy in the south of Germany, famous since medieval times for its wine and beer. For the last two years Dr. Deuerling has operated her own research group in Heidelberg. She studies chaperones, the main players in the heat shock response, proteins that control proper protein folding in cells. Her FEBS Letters paper [1] was selected as the winner of the 2005 FEBS Letters Award. “To be honest, whenl got the phone call about the award, at first I thought it was a delayed April Fool's joke. I was completely surprised.” There were several reasons. I thought it was suited to the journal in light of other papers that had been published, and it was a complete and multi-faceted story. I also wanted to publish it quickly because the chaperone field is very competitive. I was happy the paper was accepted quickly, but winning this award in addition is really motivating. That was pretty easy, I must say. During high school I was fascinated by mathematics, chemistry and biology, and in my final few years I had an excellent teacher. I was so excited about science that I decided to make it my career. I thought that being fascinated by something would be a good foundation for my profession. No, no, (emphatic) it was very clear… We try to unravel the common principles behind protein synthesis and folding, focussing on the early events in this process. In particular, we investigate (potential) chaperones that are associated with ribosomes. We use two model systems, one prokaryotic (Escherichia coli) and one eukaryotic (yeast), and we also use a variety of biochemical and genetic techniques. Actually, this work is an extension of the work I did in collaboration with Bernd Bukau on the E. coli trigger factor (TF). We made a knockout. At first we were disappointed because we didn‧t see any change in the phenotype. But we then speculated that TF might be such an important protein that the cell couldn‧t risk losing it and had a compensatory system in place. Indeed, it turned out that the DnaK chaperone system serves as a backup for TF and the simultaneous knockout of TF and DnaK in E. coli is lethal at 30 °C and higher. This was a very important finding because it was more or less the first proof that a ribosome-associated protein can be a chaperone. We published this in Nature in 1999 [2]. Oh yes. When we first presented these results, in a big chaperone conference I think, the positive feedback from many people encouraged me to continue characterising TF. Using an in vitro system we then found that TF specifically binds to one particular ribosomal protein and that this binding is crucial for TF function. This was the basis for our second Nature paper [3]. For the first time, we had clear evidence that ribosomal protein biosynthesis and the subsequent protein folding are coupled, and that TF is crucial in this process. Both of these chaperones have overlapping substrate specificities, but are mechanistically distinct; DnaK is cytosolic while TF is ribosome-bound. We think DnaK is a back-up repair system, that in the absence of TF, proteins are released from the ribosome in an unfolded or misfolded state, a situation that is recognized and corrected by DnaK. Yes, finally seeing the structure was a very exciting moment for me. When we got the call in the spring of 2004 from Nenad Ban, our collaborator, we all went to Zurich immediately, the whole group. Although we had learned a lot by studying this protein for seven years, we still had no idea how it sat on the ribosome or how it functioned. TF turned out to have this unusual and extended structure, the N- and C-termini cooperate to cradle an emerging protein in a hydrophobic pocket as it exits the ribosome. We think that TF basically acts as a protective cage to prevent nascent proteins from aggregating or degrading while folding takes place. The structure gave us new insight into the function of this chaperone. It was really incredible to see this. I don‧t think anybody expected TF to look like this. Yes, I can say that the structure was a eureka moment. I was surprised at how sophisticated nature was in designing this chaperone. I like unexpected results. It always fascinates me to see how clever nature is.