Protein Sorting in Eukaryotic Cells

Study Notes

Protein Sorting and Targeting in Eukaryotic Cells

Protein sorting and targeting involve complex processes due to the internal organization of eukaryotic cells.
The first step of protein sorting occurs during translation, while the polypeptide chain is still being synthesized.

Targeting Proteins to the Endoplasmic Reticulum

In mammalian cells, most proteins enter the ER co-translationally, whereas in yeast, both co-translational and post-translational pathways are used.
The amino acid sequence of the polypeptide chain being synthesized targets ribosomes for binding to the ER membrane.
Signal sequences, typically 15-40 amino acids long, including 7-12 hydrophobic residues, are recognized and bound by the signal recognition particle (SRP).
The SRP binds the ribosome, mRNA, and growing polypeptide chain, inhibiting further translation and targeting the complex to the rough ER.

Co-Translational Pathway

The SRP binds to the SRP receptor on the ER membrane, triggering the hydrolysis of GTP bound to the SRP, releasing the SRP from the ribosome and signal sequence.
The ribosome then binds to a protein translocation complex or translocon in the ER membrane, and the signal sequence is inserted into a membrane channel.
The growing polypeptide chain is transferred through the translocon as translation proceeds, and the signal sequence is cleaved by signal peptidase.

Insertion of Proteins into the ER Membrane

Proteins destined for the plasma membrane or membranes of compartments are initially inserted into the ER membrane instead of being released into the lumen.
Integral membrane proteins are embedded in the membrane by hydrophobic sequences that span the phospholipid bilayer.
The membrane-spanning portions of these proteins are usually α-helical regions consisting of 20-25 hydrophobic amino acids.
The hydrophobic transmembrane α helix signals a change in the translocon, causing the membrane-spanning helices of the translocon to open and allowing the hydrophobic transmembrane domain of the protein to exit the translocon laterally.

Description

Learn about the process of protein sorting in eukaryotic cells, including the role of ribosomes and the endoplasmic reticulum in targeting proteins to their destinations. Understand how proteins are synthesized and transported to different parts of the cell.