| | A model for co-translational translocation: Ribosome-regulated nascent polypeptide translocation at the protein-conducting channelEdited by Peter Brzezinski Received 7 March 2006; received in revised form 4 May 2006; accepted 8 May 2006. published online 15 May 2006. Abstract The protein-conducting channel (PCC) must allow both the translocation of soluble polypeptide regions across, and the lateral partitioning of hydrophobic transmembrane helices (TMHs) into, the membrane. We have analyzed existing structures of ribosomes and ribosome–PCC complexes and observe conformational changes suggesting that the ribosome may sense and orient the nascent polypeptide and also facilitate conformational changes in the PCC, subsequently directing the nascent polypeptide into the appropriate PCC-mediated translocation mode. The PCC is predicted to be able to accommodate one central, consolidated channel or two segregated pores with different lipid accessibilities, which may enable the lipid-mediated partitioning of a TMH from one pore, while the other, aqueous, pore allows translocation of a hydrophilic polypeptide segment. Our hypothesis suggests a plausible mechanism for the transitioning of the PCC between different configurations. Abbreviations: CFAD, cytosolic factor-associating domain, EM, electron microscopy, FSC, Fourier shell correlation, NMFF, normal mode-based flexible fitting, NPS, nascent polypeptide signal, PCC, protein-conducting channel, RMSD, root mean squared difference, RNC, ribosome–nascent polypeptide complex, rRNA, ribosomal RNA, TMH, transmembrane helix a Howard Hughes Medical Institute, Health Research, Inc. at the Wadsworth Center, Empire State Plaza, Albany, NY 12201-0509, USA b Department of Biomedical Sciences, State University of New York at Albany, Empire State Plaza, Albany, NY 12201-0509, USA  Corresponding author.
PII: S0014-5793(06)00609-0 doi:10.1016/j.febslet.2006.05.019 © 2006 Federation of European Biochemical Societies | |
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ABSTRACT
