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These two concepts seem almost contradictory, proteins have a net negative charge due to the amino acids in them each having a small negative charge, yet membrane proteins are able to exist traversing the plasma membrane, which is impermeable to charged molecules (hence the need for membrane proteins).

How do these two statements remain true simultaneously?

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    $\begingroup$ which small charges are you referring to? The trans-membrane parts are usually made out of hydrophobic amino acids that don't have a significant charge. $\endgroup$
    – Mad Scientist
    Oct 8, 2012 at 11:33
  • $\begingroup$ So does the overall charge on the macromolecule not have any effect if part of it is uncharged? $\endgroup$
    – Matthew Higgins
    Oct 8, 2012 at 11:35
  • $\begingroup$ And, building on that, how does the charged element of the protein pass through the membrane after synthesis to create a protein which protrudes through both sides of the membrane? $\endgroup$
    – Matthew Higgins
    Oct 8, 2012 at 11:45
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    $\begingroup$ Just a minor comment on the background part of the question: the net charge on a protein will depend on the pH, and is certainly not always negative. Similarly the charges on individual amino acids will vary, but again are not always negative. So for example lysine and arginine side chains are positively charged unless the pH is very high. This is why histones (rich in these residues) are positively charged at physiological pH, thus interacting with negatively charged DNA. $\endgroup$
    – Alan Boyd
    Oct 8, 2012 at 13:56

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Transmembrane proteins are inserted into the membrane in the ER in a rather complicated system, there is a whole chapter about translocation of proteins in "Molecular Biology of the Cell".

The proteins are moved through an aqueous pore in the Sec61 complex, which explains how charged parts of a protein are moved across the membrane.

The parts of a transmembrane protein that remain in the membrane are usually composed of hydrophobic amino acids that aren't charged.

I strongly recommend you to read up on the whole translocation stuff in a cell biology book like the Alberts I linked. There's a lot more to it than what I wrote here.

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  • $\begingroup$ Also, lipoproteins use covalently bound lipids to anchor to the membrane. $\endgroup$
    – R Stephan
    Oct 9, 2012 at 6:58

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