My university supervisor said that the signal sequence is always cleaved, however my text book differs.

What I gather from my text book (though it isn't very clearly stated so i'm not sure) is that:

  • A protein that is meant to be completely extracellular (or go into a membrane-bound organelle) will have only a signal sequence which will be cleaved by signal peptidase.
    • If there is a protein that is meant to have just one transmembrane domain, it can either:

a) have a single signal sequence, however this will not be at the start of the N terminus that is being translated. If there are more negatively charged amino acids before the signal sequence, then when the signal sequence binds into the translocon complex this beginning 'tail' will be threaded through as it is repelled from the more negatively charged cell interior. The amino acids following the sequence will be more positively charged to stay in the cytosol rather than passing through to the ER lumen. This will determine the directionality of this single-transmembrane-domain strand. //Alternatively there can be one signal sequence and the amino acids before are more positively charged and after are more negatively charged, so you get the reverse situation where the already synthesised strand remains in the cytosol and the rest of the polypetide is threaded through as it is synthesised. Either way, this involves just one signal sequence.

b)The polypeptide can have one signal sequence and one stop-transfer sequence, with the charges on the surrounding amino acids determining directionailty, and then one of the signal sequcne or stop transfer sequence may be cleaved by signal peptidase.

  • Multipass proteins have a series of signal peptides/start-transfer and stop transfer.

But if my textbook (or rather what I understand from it!) is correct, then some but not all signal sequences are cleaved. So how does the signal peptidase know which to cleave?

I would really appreciate if someone could tell me answer this and also correct me where I have gone wrong in my understanding.

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    $\begingroup$ Would you mind providing a source/page number for the text so I could take a look at it? Having a multitude of transfer signals makes sense to me, but I don't understand the rationale for having multiple SRP-binding sequences. $\endgroup$ – kingfishersfire Dec 13 '16 at 16:43
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    $\begingroup$ @kingfishersfire I am using molecular biology of the cell 6th edition, Albert's et al (Garland Science). I do not know where one can get the 6th edition online-I have a hard copy- however I have found the corresponding chapter for the fourth edition ncbi.nlm.nih.gov/books/NBK26878 $\endgroup$ – 21joanna12 Dec 13 '16 at 17:24
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    $\begingroup$ I couldn't find the section you were talking about in that text, however I did find this zoology.ubc.ca/~berger/B200sample/unit_8_protein_processing/… that looks like it might be helpful for you. $\endgroup$ – kingfishersfire Dec 13 '16 at 17:44
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    $\begingroup$ This is a rather long question, and I'm still not sure what exactly you're asking. Are you asking what makes a SP different to a TMH, or are there exceptions to SP cleavage? As far as I've understood the topic, signal peptides should be cleaved; it's part of their definition. If not, then there isn't too much distinguishing them from any other TMH post insertion. With a more specific question, I can provide a specific answer. $\endgroup$ – James Dec 14 '16 at 1:36

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