DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

The lab is interested in how proteins cross membranes, how they fold, and how they are modified, particularly how dilsulfide bridges are formed. We have determined the X-ray structure of the protein-conducting channel that allows proteins to move from the cytosol across the ER membrane or to integrate into the membrane. We are now using the structure to adress the mechanism of protein translocation in more detail. Another project in the lab concerns the mechanism by which proteins are transported from the ER lumen back into the cytosol (retro-translocation). Finally, we are interested in the mechanism by which dilsulfide bridges are formed and by which wrongly formed disulfide bridges are corrected. In particular, we wish to determine the X-ray structure of a homolog of an enzyme that moves reduction equivalents across the membrane (CcdA). 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.

Publications

• Ye J, Osborne AR, Groll M, Rapoport TA.RecA-like motor ATPases--lessons from structures.Biochim Biophys Acta 2004 Nov 4;1659(1):1-18.
  15511523
• Rapoport TA, Goder V, Heinrich SU, Matlack KE.Membrane-protein integration and the role of the translocation channel.Trends Cell Biol 2004 Oct;14(10):568-75.
  15450979
• Ye Y, Shibata Y, Yun C, Ron D, Rapoport TA.A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol.Nature 2004 Jun 24;429(6994):841-7.
  15215856
• Van den Berg B, Clemons WM, Collinson I, Modis Y, Hartmann E, Harrison SC, Rapoport TA.X-ray structure of a protein-conducting channel.Nature 2004 Jan 1;427(6969):36-44.
  14661030
• Tsai B, Gilbert JM, Stehle T, Lencer W, Benjamin TL, Rapoport TA.Gangliosides are receptors for murine polyoma virus and SV40.EMBO J 2003 Sep 1;22(17):4346-55.
  12941687
• Heinrich SU, Rapoport TA.Cooperation of transmembrane segments during the integration of a double-spanning protein into the ER membrane.EMBO J 2003 Jul 15;22(14):3654-63.
  12853480
• Ye Y, Meyer HH, Rapoport TA.Function of the p97-Ufd1-Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains.J Cell Biol 2003 Jul 7;162(1):71-84.
  12847084