Ribosome-channel complexes play a critical role in the biogenesis of secretory proteins and resident proteins of the ER and Golgi. RCCs also mediate the lateral integration of nascent membrane proteins into the lipid bilayer of the ER membrane. We are studying this process using specimens from eukaryotes and bacteria. In our studies, we find that an initial contact with L23e and helix 50 on the large subunit may be made by the channel subunit (Sec61). A complete channel may then assemble under the ribosome with displacement of the SRP-SR complex. As a step towards a complete model of the co-translational translocon, we have recently created a complete homology model of the canine ribosome, based on a map at ~8.0 Å resolution. Finally, other components are recruited to the translocon to interact with the nascent chain, such as TRAP and TRAM, or to modify the polypeptide (OST, SPC). Structures of these components alone or with Sec61 are needed in order to understand how they interact within the translocon and to decipher how nascent proteins are handled during co-translational translocation.