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
• Shibata Y, Voss C, Rist JM, Hu J, Rapoport TA, Prinz WA, Voeltz GK.The reticulon and DP1/Yop1p proteins form immobile oligomers in the tubular endoplasmic reticulum.J Biol Chem 2008 Apr 28.
  18442980
• Goder V, Carvalho P, Rapoport TA.The ER-associated degradation component Der1p and its homolog Dfm1p are contained in complexes with distinct cofactors of the ATPase Cdc48p.FEBS Lett 2008 May 14;582(11):1575-80.
  18407841
• Erlandson KJ, Or E, Osborne AR, Rapoport TA.Analysis of polypeptide movement in the SecY channel during SecA-mediated protein translocation.J Biol Chem 2008 Mar 21.
  18359943
• Hu J, Shibata Y, Voss C, Shemesh T, Li Z, Coughlin M, Kozlov MM, Rapoport TA, Prinz WA.Membrane proteins of the endoplasmic reticulum induce high-curvature tubules.Science 2008 Feb 29;319(5867):1247-50.
  18309084
• Burton BM, Marquis KA, Sullivan NL, Rapoport TA, Rudner DZ.The ATPase SpoIIIE transports DNA across fused septal membranes during sporulation in Bacillus subtilis.Cell 2007 Dec 28;131(7):1301-12.
  18160039
• Menetret JF, Schaletzky J, Clemons WM Jr, Osborne AR, Skanland SS, Denison C, Gygi SP, Kirkpatrick DS, Park E, Ludtke SJ, Rapoport TA, Akey CW.Ribosome binding of a single copy of the SecY complex: implications for protein translocation.Mol Cell 2007 Dec
  18158904
• Palazzo AF, Springer M, Shibata Y, Lee CS, Dias AP, Rapoport TA.The signal sequence coding region promotes nuclear export of mRNA.PLoS Biol 2007 Dec;5(12):e322.
  18052610
• Rapoport TA.Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes.Nature 2007 Nov 29;450(7170):663-9.
  18046402
• Ye J, Cho SH, Fuselier J, Li W, Beckwith J, Rapoport TA.Crystal structure of an unusual thioredoxin protein with a zinc finger domain.J Biol Chem 2007 Nov 30;282(48):34945-51.
  17913712
• Or E, Rapoport T.Cross-linked SecA dimers are not functional in protein translocation.FEBS Lett 2007 Jun 12;581(14):2616-20.
  17511989
• Carvalho P, Goder V, Rapoport TA.Distinct Ubiquitin-Ligase Complexes Define Convergent Pathways for the Degradation of ER Proteins.Cell 2006 Jul 28;126(2):361-73.
  16873066