The structural and functional coupling of two molecular machines, the ribosome and the translocon

Abstract

Ribosomes synthesizing secretory and membrane proteins are bound to translocons at the membrane of the endoplasmic reticulum (ER). Both the ribosome and translocon are complex macromolecular machines whose structural and functional interactions are poorly understood. A new study by Pool (Pool, M.R. 2009. J. Cell Biol. 185:889-902) has now shown that the structure of the translocon is dictated by the identity of the protein being synthesized by the ribosome, thereby demonstrating that the two macromolecular machines are structurally coupled for functional purposes. The study also identifies an unexpected component in the apparent molecular linkage that connects the two machines, a discovery that shows the current view of translocon structure is oversimplified.

Figure 1.

Nascent chain control of translocon structure from inside the ribosome. (A and B) A nascent secretory protein is fully extended during synthesis (A), whereas the TMS in a nascent membrane protein (B) folds into an α-helix upon reaching a tunnel constriction formed by Rpl4 and Rpl17. Although Sec61β is always adjacent to Rpl17 in an RTC, RAMP4 is recruited to the RTC and is cross-linked to Rpl17 only when a TMS reaches the constriction. The cross-linking of Rpl17 to a TMS and to RAMP4 coincides with the BiP-mediated closure (either directly, as depicted, or indirectly) of the lumenal end of the aqueous pore and the subsequent opening of the ion-tight ribosome–translocon junction (depicted by a tilting of the ribosomal subunit). PTC, peptidyl transferase center.