Submitted on July 1, 2009
Accepted on October 21, 2009
Structure of Monomeric Yeast and Mammalian Sec61 Complexes Interacting with the Translating Ribosome
Thomas Becker 1, Shashi Bhushan 1, Alexander Jarasch 1, Jean-Paul Armache 1, Soledad Funes 2, Fabrice Jossinet 3, James Gumbart 4, Thorsten Mielke 5, Otto Berninghausen 1, Klaus Schulten 4, Eric Westhof 3, Reid Gilmore 6, Elisabet Mandon 6*, Roland Beckmann 1*
1 Gene Center Munich and Center for Integrated Protein Science CIPSM, Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
2 Gene Center Munich and Center for Integrated Protein Science CIPSM, Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany.; Departamento de Bioquímica, Instituto de Fisiología Celular, Circuito Exterior S/N, Ciudad Universitaria, Universidad Nacional Autónoma de México, Mexico, D.F., 04510, Mexico.
3 Institut de Biologie Moléculaire et Cellulaire du CNRS, UPR9002, Architecture et Réactivité de l’ARN, Université Louis Pasteur, 15 rue René Descartes, F-67084 Strasbourg, Cedex, France.
4 Department of Physics, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
5 Ultrastrukturnetzwerk, Max Planck Institute for Molecular Genetics, Ihnestr. 63-73, D-14195 Berlin, Germany; Institut für Medizinische Physik und Biophysik, Charite–Universitätsmedizin Berlin, Ziegelstrasse 5-9, 10117-Berlin, Germany.
6 Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
* To whom correspondence should be addressed.
Elisabet Mandon , E-mail: elisabet.mandon{at}umassmed.edu
Roland Beckmann , E-mail: beckmann{at}lmb.uni-muenchen.de
The trimeric Sec61/SecY complex is a protein-conducting channel (PCC) for secretory and membrane proteins. Although Sec complexes can form oligomers, it has been suggested that a single copy may serve as an active PCC. We determined subnanometer resolution cryo-electron microscopy structures of eukaryotic ribosome-Sec61 complexes. In combination with biochemical data we found that in both idle and active states, the Sec complex is not oligomeric and interacts mainly via two cytoplasmic loops with the universal ribosomal adaptor site. In the active state, the ribosomal tunnel and a central pore of the monomeric PCC were occupied by the nascent chain contacting loop 6 of the Sec complex. This provides a structural basis for the activity of a solitary Sec complex in cotranslational protein translocation.
