Endoplasmic Reticulum

ID #2270

I was wondering if I could get something clarified. In the lecture, it says that if the first presented signal is an internal signal peptide, then the N terminus is in the cytoplasm and the C-terminus is in the lumen. In the book, it says that the C-terminus could either be in the lumen or cytoplasm. Did Brad say how we recognize the difference between these two? I know he said that if the first presented signal is an N-terminal signal peptide, then the N-terminus would be in the lumen. And if the first presented signal was an internal signal peptide, the N-terminus would be in the cytoplasm.


The important part here is that you understand the purpose of each signal, how it's positioned in the translocon and what that means for the orientation of the protein as a whole. The first question that you should ask when answering questions about the orientation of a protein being synthesized in the RER is "What is the first signal presented"? Then this is followed by "are there any other signals presented after the first one?" 
You were right when you said that "if the first presented signal is an N-terminal signal peptide, then the N-terminus would be in the lumen. And if the first presented signal was an internal signal peptide, the N-terminus would be in the cytoplasm." Now, the orientation of the C-terminus would depend on whether or not another signal is presented. Let's break it down into these scenarios:
IA. Is the 1st signal an N-ter or amino-terminal signal peptide?
If yes, N-terminal end of the protein will be in the lumen of the ER
If no, scroll down to IIA.
IB. Is there a second signal (a stop transfer sequence)?
If yes, the C-terminal end will be in the cytoplasm
If no, the protein will be in the lumen of the ER as a soluble protein (not integrated in the membrane)
IIA. Is the 1st signal an internal signal peptide?
If yes, the N-terminal end of the protein will be in the cytoplasm
If no, scroll up to IA
IIB. Is there a second signal (a stop transfer sequence)?
If yes, the C-terminal end of the protein will be in the cytoplasm (this will be a 2-pass transmembrane protein)
If no, the C-terminal end will be in the lumen of the ER (this will be a single-pass transmembrane protein)
 

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