Research Abstract

The lab is interested in how proteins cross membranes. We have determined the X-ray structures of the protein-conducting SecY/Sec61 channel that allows proteins to move from the cytosol across the membrane or to integrate into it. We have also determined a crystal structure of the SecY channel in complex with the SecA ATPase that pushes polypeptides through the channel. We are now using the structures to address the mechanism of protein translocation in more detail. Another project in the lab concerns the mechanism by which misfolded ER proteins are transported back into the cytosol and degraded by the proteasome (ERAD or retro-translocation). Finally, we are interested in the mechanisms by which the ER achieves its characteristic morphologies. We have identified proteins that shape tubules and sheets, fuse ER membranes, and generate tubular junctions. All these projects have a high relevance to cancer research. For example, our research addresses how growth factors are secreted from cells and how tyrosine kinases are integrated into membranes.