Protein Processing I:  Targeting to the Endomembrane System

Overview of the Endomembrane System:The Endomembrane system is a complex of membrane limited compartments involved in the processing and movement of proteins. Newly synthesized proteins enter the endomembrane system through the endoplasmic reticulum. From there them move through the Golgi apparatus and into either the Secretory Pathway or the Lysosomal Pathway.

We begin by looking at targeting of proteins from the cytosol to the endoplasmic reticulum.


1. Targeting to the endoplasmic reticulum.


Synthesis of proteins entering the endoplasmic reticulum is initiated on free ribosomes. 

A targeting sequence of  hydrophobic amino acids near the N- terminal end of the growing polypeptide results in the binding of the ribosome to ER membrane and in insertion of the polypeptide into the endoplasmic reticulum.

Proteins going to Golgi, endosomes, lysosomes and ER all enter the ER and don't come out again.

Two groups of proteins are targeted to the ER:

Let's deal first with the case of proteins that will be inserted into the ER lumen:

14_13.jpg (41540 bytes)  Figure 14-13.  Animation of co-translational insertion of protein into lumen of ER

Proteins inserted into membranes:

14_15.jpg (63028 bytes)
Figure 14-15. 

Animation of insertion of a single pass membrane protein with N terminal end in ER lumen

Import of a membrane protein into the membrane of the ER. The blue sheath-like component shown in the figure is the translocation channel that moves the protein through the membrane. Notice that the Stop Transfer sequence (orange) results in the disassembly of the translocation channel. Note that the signal sequence at the N terminal end of the protein is cleaved off, releasing the N terminal portion of the protein into the ER lumen.  This example is a single pass membrane protein that contains a single membrane crossing domain (the stop transfer signal).
This diagram shows the relation between translocation control sequences (signal sequences, start transfer sequences, stop transfer sequences) and the arrangement of the protein in the membrane. 

How would the translocation control sequences have to be arranged to get the N terminal end of  the protein on the cytoplasmic side? - to get the C terminal end of the protein on the cytoplasmic side?

Link to animations of co-translational insertion of proteins (5 different cases).