15.5:
Protein Translocation Machinery on the ER Membrane
In the ER, protein translocation across the membrane occurs via the embedded protein complex called the translocon.
It encompasses a core protein-conducting Sec61 complex and other accessory protein complexes that associate with Sec61 constantly or temporarily when required.
The Sec61 complex has a main vertical channel secured by a short α helix that acts as a plug and opens and closes as required.
It allows hydrophilic protein segments to translocate into the ER lumen.
Sec61 also has a lateral gate that opens like a clamshell to transfer hydrophobic domains of transmembrane proteins into the ER membrane.
Close to the Sec61 channel, integral membrane proteins, Sec62 and Sec63 form a subcomplex. They assist in the post-translational translocation of some secretory proteins.
The oligosaccharyltransferase complex is also an integral translocon component that adds complex sugar molecules to specific residues of a polypeptide to form a glycoprotein.
Other complexes like the signal peptidase transiently associate with the Sec61 channel to cleave the signal peptide from the polypeptide chain.
15.5:
Protein Translocation Machinery on the ER Membrane
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex. In higher eukaryotes, such as mammals, the channel is capped in its resting state to prevent the leakage of ions like calcium into the cytosol.
Accessory protein complexes associated with the Sec61 channel
Sec62 and Sec63 are integral transmembrane proteins associated with the Sec61 complex. They are primarily involved in the functioning of the Sec61 channel's lateral gate and aid in the exit of the signal sequence and transmembrane domains into the lipid bilayer.
The translocon-associated protein or TRAP complex is a hetero-tetrameric constitutive subunit of the translocon complex, present behind the Sec61 channel. It assists in the binding of signal peptides having low hydrophobicity to the Sec61 channel. The oligosaccharyltransferase (OST) complex is another closely associated complex, which transfers pre-assembled glycans to select asparagine residues.
Some proteins, like the signal peptidase complex, associate with the translocon complex under specific conditions. For instance, the signal recognition particle receptor (SR) only interacts with the Sec61 channel to hand over the ribosome-nascent peptide complex during active translocation. Other proteins like lectin chaperones (calnexin and malectin) and sensor molecules (IRE1) associate with the translocon to correctly fold the incoming polypeptide or signal misfolded proteins.
Suggested Reading
- Gemmer, Max, and Friedrich Förster. "A clearer picture of the ER translocon complex." Journal of cell science 133, no. 3 (2020): jcs231340.