MoBio Sorting of Proteins Chapter 5

As discussed in the previous section, proteins are synthesized on ribosomes which are located mainly in the cytosol. Only a small number of ribosomes are located in mitochondria and chloroplasts. Proteins synthesized on these ribosomes can be directly incorporated into the compartments within these organelles. However, most mitochondrial and chloroplast proteins are encoded by nuclear DNA and synthesized on cytosolic ribosomes. These and all other proteins synthesized in the cytosol must be transported to appropriate locations in the cell. This is made possible by the specific signal sequence in the newly synthesized peptide.

Image

Figure 5-D-1. Protein sorting.

  1. If the N terminus of the new peptide contains a stretch of hydrophobic residues, it is sent to the rough endoplasmic reticulum (ER) for further sorting. Otherwise, it goes to non-ER pathways.
  2. The new peptide is retained in the rough ER if its C-terminus contains the sequence "Lys-Asp-Glu-Leu" (KDEL in one-letter code). Otherwise, it will move to the Golgi apparatus.
  3. Proteins containing a specific transmembrane α helix will be localized in the Golgi apparatus.
  4. After glycosylation at the Golgi apparatus, the modified protein containing a mannose 6-phosphate (M6P) will be delivered to the lysosome.
  5. Proteins that can aggregate with chromogranin B (secretogranin I) or secretogranin II will be sorted into regulated secretory vesicles where proteins are released upon specific stimulation. Otherwise, they are sorted into another type of vesicles which continuously move to the plasma membrane or outside the cell.

Non-ER pathways:

Nucleus

Nuclear Transport

Mitochondria and Chloroplast

Book Section:

Synthesis and Targeting of Mitochondrial and Chloroplast Proteins - From Molecular Cell Biology by Lodish et al.

Peroxisome

Signal sequence: "Ser-Lys-Leu" (SKL in one-letter code) at the very C-terminus.