Protein Translocation by the Sec61/Secy Channel

Abstract

The conserved protein-conducting channel, referred to as the Sec61 channel in eukaryotes or the SecY channel in eubacteria and archaea, translocates proteins across cellular membranes and integrates proteins containing hydrophobic transmembrane segments into lipid bilayers. Structural studies illustrate how the protein-conducting channel accomplishes these tasks. Three different mechanisms, each requiring a different set of channel binding partners, are employed to move polypeptide substrates: The ribosome feeds the polypeptide chain directly into the channel, a ratcheting mechanism is used by the eukaryotic endoplasmic reticulum chaperone BiP, and a pushing mechanism is utilized by the bacterial ATPase SecA. We review these translocation mechanisms, relating biochemical and genetic observations to the structures of the protein-conducting channel and its binding partners.

Ribosome Binding to and Dissociation from Translocation Sites of the Endoplasmic Reticulum Membrane

“…This complex binds to the ER membrane by interactions between SRP and the SRP receptor (SR) and between the ribosome and the Sec61 complex, a heterotrimeric membrane protein that forms a proteinconducting channel (Van den Berg et al, 2004). The nascent polypeptide chain forms a loop when inserting into the channel, with the signal or TM sequence intercalated into the walls of the channel and the following mature region in the pore proper (for reviews, see Rapoport et al, 2004;Osborne et al, 2005). For secretory proteins, this part of the elongating chain is moved through the channel into the ER lumen, and the signal sequence is eventually cleaved off.…”

Membrane topology and post‐translational modification of the Saccharomyces cerevisiae essential protein Rot1

“…The translocation of polypeptides into the endoplasmic reticulum occurs at the translocon, a poreforming structure (Osborne, 2005). In yeast, the targeting of proteins to the translocon can occur by two distinct pathways: the major signal recognition particle (SRP)-dependent mechanism that occurs co-translationally and requires SRP and its membrane-bound receptor, or an SRP-independent mechanism that is capable of an efficient posttranslational targeting of polypeptides to the ER membrane.…”

“…In eukaryotic cells, protein translocation to the endoplasmic reticulum occurs at the translocon or Sec61 complex, a pore-forming structure that orchestrates the transport and maturation of polypeptides at the ER membrane (for a review, see Osborne et al, 2005). In yeast, the targeting of membrane proteins precursors to the translocon can occur by two distinct pathways (Wilkinson et al, 1997): a signal recognition particle (SRP)-dependent co-translational pathway, and an alternative SRP-independent pathway that is capable of an efficient post-translational translocation of completed polypeptide chains.…”

Assembly pathway of a bacterial complex iron sulfur molybdoenzyme

“…The bacterial Sec translocase is composed of a membrane embedded protein conducting channel (PCC) that consists of three integral membrane proteins, SecY, SecE, and SecG, and a peripheral associated ATPase, SecA, which functions as a molecular motor to drive membrane translocation (120,123,127). SecA associates peripherally to the PCC, where it accepts secretory proteins from chaperones to subsequently thread the unfolded protein through the narrow PCC transmembrane channel in an ATP dependent fashion.…”