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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.

Tags
Protein Translocation MachineryER MembraneTranslocon ComplexSec61 ComplexSec62Sec63TRAP ComplexOligosaccharyltransferase OST ComplexSignal Peptidase ComplexSignal Recognition Particle Receptor SRCalnexinMalectinIRE1

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