Post-translational Translocation of Proteins to the RER

Some proteins are completely synthesized by free ribosome particles in the cytosol before entering the ER lumen. This mechanism is called post-translational protein translocation.

After translation, the cytosolic chaperones immediately bind to the polypeptide chain to prevent it from folding prematurely.

Once the chaperone-bound protein reaches the ER membrane, its signal sequence is recognized by a recognition site within the Sec61 channel.

Then, the protein slowly begins to glide down the channel and emerges at the luminal end, where it recruits ATP-bound BiP chaperone.

The heterodimeric Sec62/Sec63 complex hydrolyzes the ATP to induce a conformational change in the BiP molecule, allowing it to clasp the polypeptide.

New BiP molecules keep attaching to the incoming polypeptide, actively pulling it down into the ER lumen.

As the polypeptide enters the lumen, its signal sequence is cleaved off by the signal peptidase located in the ER membrane.

On completion of translocation, the nucleotide exchange factors replace all the ADPs bound to the BiP molecules with ATPs, preparing them for the next cycle of protein translocation.