is subsequently delivered at the Sec61 channel embedded into the endoplasmic membrane. After transfer of the nascent chain to the Sec complex, translation continues and the polypeptide is pushed through the translocation channel (1). Secretory proteins with a moderately hydrophobic signal sequence escape recognition by the SRP system and are therefore funneled into the post-translational pathway. These proteins are kept in an unfolded state after release from the ribosome through association with cytosolic chaperones, which also target the polypeptide to the Sec channel. Following capture of the substrate protein by the Sec61 channel, the polypeptide is bound by the luminal Hsp70 chaperone BiP which prevents it’s backsliding into and in fact “pulls” the substrate into the lumen (2). Although both pathways converge at the Sec61 channel, both translocation modes require a structurally different Sec61 complex. In yeast, co-translational translocation is performed by the Sec61 complex made up of Sec61, Sss1 and Sbh1, while, during post-translational translocation the Sec61 channel associates with another membrane protein complex, known as the Sec62/Sec63 complex (2). This represents a tetrameric complex comprising Sec62, Sec63, Sec71 and Sec72. Of these, Sec62 and 63 are essential for cell viability unlike Sec71 and 72. These proteins are not found in mammals, while in humans, Sec62 and 63 are frequently mutated or over expressed in different tumors. The molecular details of the co-translational pathway are reasonably well understood, in contrast to post-translational translocation. This is primarily caused by a lack of structural information and with regards to this the recently determined atomic structures of the post-translational Sec complex from yeast (5,6) are of great importance because they provide mechanistic insight into post-translational protein export.
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