Translocation Gets a Push Minireview

Recent years have seen a remarkable concordance of observations concerning the mechanism of polypeptide translocation during secretion in bacteria and in eukaryotic cells. All organisms have some form of signal recognition particle, and diverse membranes from the Escherichiacoli inner membrane through the yeast and mammalian endo. plasmic reticulum (ER) have a trimeric integral membrane protein complex that comprises the channel or translocase through which nascent secretory polypeptide chains are transmitted. In E. coli, the translocase consists of three genetically and biochemically defined molecules: SecY, SecE, and Band 1 (now called SecG) (Schatz and Beck-with, 1990; Brundage et al., 1992; Douville et al., 1994). In yeast and mammals, the corresponding complex contains Sec6lp and two other subunits that in mammalian cells are called Sec61 8 and y (Hartmann et al., 1994). Two of the three subunits of the translocase are homologous in all three sources (Hartmann et al., 1994). A hydrophilic channel activity, with significant connections to the poly-peptide translocase, has been detected in E. coli inner membrane and mammalian ER membrane fractions (Si-mon and Blobel, 1991, 1992; Crowley et al., 1994). Although the proof is not yet in hand, it seems probable that the channel activity is formed by the SecY and Sec61 complexes. The most extensive enzymologic dissection of the trans-locase has been achieved for the SecY complex, where the Wickner(Brundageet al., 1992) and Mizushima(NishC yama et al., 1993) groups have purified the functional entity and reconstituted translocation activity in proteolipo-somes using the intact oligomer or from isolated subunits. A direct contact between the nascent secretory chain pro-OmpA and the SecY subunit has been established by chemical cross-linking experiments (Joly and Wickner, 1993). In eukaryotic ER membranes, cross-linking experiments identify Sec61 as a partner of nascent secretory chains that are engaged to the translocase either by post-translational or cotranslational insertion (Giirlich et al. Divergence of Translocation Mechanisms Of course, nature has not been so simple, or boring, as to have conserved the translocation mechanism completely. Possibly significant differences in the coupling of translation to translocation, in the choice of energy sources to drive the process, and in the full set of proteins necessary to complete the event have been detected. The issue of post-versus cotranslational translocation of secretory proteins is not as contentious as in years past because it appears that examples of both are known. The difference is that organisms deploy one or the other pathway in varying …