Polypeptide Translocation: A Pretty Picture Is Worth a Thousand Words

Randy Schekman coli (Ito, 1984), that forms a complex with two other membrane proteins together comprising the core trans-Sec61p presents a surface across which secretory poly-peptides pass. First, nascent chains trapped at various stages in transit through the membrane could be chemically crosslinked to Sec61p (Mü sch et al., 1992; Sanders In a short note published in 1971, and in a detailed et al., 1992). Second, the entire translocation process biochemical investigation published in 1975 (Blobel and was reproduced with pure Sec61/SecY complex recon-Gö rlich and Rapoport, 1993). veloped the signal hypothesis and thus initiated the A Channel Revealed modern era in studies on secretory polypeptide biogen-Although these studies predict the existence of a pore esis. In its simplest form the model posits a role for created by the Sec61p complex, few would have an N-terminal signal that directs the nascent secretory guessed that the channel could be seen simply by chain and ribosome to a polar channel in the ER mem-spreading a detergent solution of pure protein on a mi-brane through which the elongating polypeptide could croscope grid! Images presented by Hanein et al., 1996 be transmitted into the lumenal space. In the ensuing (see Figure 1) show oligomeric complexes each assem-decades, a number of biochemical, genetic, and bio-bled from 3–4 mammalian Sec61p trimers surrounding physical approaches were developed to identify the a ‫02ف‬ A ˚ pore seen in the electron microscope either by components of the translocation machinery and to negative staining or in rapidly frozen, unstained speci-probe the environment of the putative channel in the ER mens. A variation on this theme is seen with the yeast membrane. Two major themes of progress, isolation of Sec61p complex which includes four additional subunits the membrane proteins (the Sec61p complex) involved whose role is to present secretory chains that are post-in polypeptide transit, and the detection of channel ac-translationally translocated through the channel. Here, tivity relevant to the translocation event, have pro-the image of a channel is seen occasionally, but most gressed in parallel. In a " signal " paper in this issue of of the time the yeast complex adheres to the grid about Cell (Hanein et al., 1996), these two themes have now an axis that is not uniformly perpendicular. been joined in dramatic form with the demonstration of Equally dramatic images are seen when the mamma-a pore formed by the assembly of Sec61p complexes lian and …