Summary:

During the process of co-translational protein translocation, nascent polypeptide chains bearing a signal sequence are transferred across or inserted into lipid bilayers by specialized machinery known as the translocon. This requires a direct interaction between the ribosome and the membrane-bound translocon and involves the passage of the nascent chain from the ribosomal exit tunnel into the translocon pore. Due to the universality of this process, translocons from different domains of life all comprise the same conserved heterotrimeric cores, referred to as SecYEG or Sec61p complexes. While considerable progress has been made over the last few years in advancing our knowledge of protein translocation, an understanding of its basic molecular mechanism will require structural information on complexes between the ribosome and SecYEG/Sec61p, both in the presence and absence of a nascent polypeptide chain. Currently, the only structural data available for these complexes is in the form of low resolution models derived by electron microscopy, making it impossible to grasp the translocation process in all but the most general terms. Thus, we propose to investigate the structure of complexes between translating and non-translating 70S ribosomes or 50S ribosomal subunits and heterotrimeric SecYEG/Sec61p complexes by X-ray crystallography, in the hope of capturing the translocon pore in both 'open' and 'closed' states. Together, these structures would provide a detailed picture of the translocation process and the mechanism by which proteins are targeted for secretion or insertion into membranes.
 

Papers relating to this work:

Mitra K., Schaffitzel C., Shaikh T., Tama F., Jenni S., Brooks C.L. 3rd, Ban N., Frank J. (2005). Structure of the E. coli protein-conducting channel bound to a translating ribosome. Nature 438 : 318-24.

Van den Berg B., Clemons W.M. Jr, Collinson I., Modis Y., Hartmann E., Harrison S.C., Rapoport T.A. (2004). X-ray structure of a protein-conducting channel. Nature 427 : 36-44.

Osborne A.R., Rapoport T.A., van den Berg B. (2005). Protein translocation by the Sec61/SecY channel. Annu Rev Cell Dev Biol. 21 : 529-50.