Protein Translocation into the Endoplasmic Reticulum

The targeting process is highly efficient and usually occurs via co-translational translocation, meaning the protein begins threading through the ER membrane while it is still being synthesized by the ribosome.

The Targeting Machinery

To move a protein from the cytosol to the ER, the cell employs a specialized targeting system:

1. Signal-recognition particle (SRP): As the ER signal sequence emerges from the ribosome, the SRP binds to both the signal sequence and the ribosome. This binding temporarily slows down protein synthesis, preventing the protein from folding prematurely in the cytosol.
2. SRP receptor: The SRP-ribosome complex then migrates to the ER membrane, where the SRP binds to its specific SRP receptor.
3. Protein Translocator: Once docked, the SRP is released, and the ribosome is passed to a protein translocator (a channel spanning the ER membrane). The ribosome resumes translation, and the mechanical force of the growing polypeptide chain pushes the protein through the translocator channel.

Exam Tip: Remember that translocation into the ER is often co-translational. This is a key distinction from the transport of proteins into the nucleus, where proteins are transported in their fully folded state.

Pathways for Different Protein Types

The mechanism of translocation diverges depending on whether the protein is meant to be a soluble resident of the ER or a permanent part of the membrane.

1. Water-Soluble Proteins

Water-soluble proteins are destined to reside entirely within the ER lumen. As the polypeptide is pushed through the translocator, a specialized enzyme called signal peptidase recognizes the signal sequence and cleaves it from the growing chain. Once translation is complete, the mature, soluble protein is released into the lumen.

2. Transmembrane Proteins

Transmembrane proteins are designed to be embedded within the lipid bilayer. These proteins possess the standard ER signal sequence but also contain additional hydrophobic segments known as stop-transfer sequences.

When a stop-transfer sequence enters the protein translocator, it signals the channel to halt the translocation of the polypeptide into the lumen. Instead of continuing through the channel, the hydrophobic segment is released sideways into the lipid bilayer. This mechanism ensures the protein remains anchored in the membrane with a specific orientation, such as having its N-terminus in the lumen and its C-terminus in the cytosol.

Summary Table: Translocation Comparison

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Key Terms Review:

• Translocation: The movement of proteins across a membrane.
• Cytosol: The aqueous component of the cell surrounding the organelles.
• Lumen: The internal space of a membrane-bound organelle like the ER.