Why do GPCRs loop 7 times? Watch

Scienceisgood
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Hey Guys;

Well, after finishing my drug receptors revision, I understand pretty much everything except why the GPCR loops through the cell membrane 7 times.

Why?
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thegodofgod
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(Original post by Scienceisgood)
Hey Guys;

Well, after finishing my drug receptors revision, I understand pretty much everything except why the GPCR loops through the cell membrane 7 times.

Why?
Very interesting question!

In short, it seems that the simple answer is 'evolution', i.e. that's just how we have evolved. I read around a bit as I didn't know the answer myself, and there are some theories. It has been suggested that an odd number of TM domains allows the N-terminus of the polypeptide to be on the extra-cellular side and the C-terminus to be on the intra-cellular side of the cell membrane. The more relevant suggestion, however, is that having 7 TM domains allows structural stability and functional diversity. Although this somewhat conflicts the fact that some in vivo functional GPCRs do, in fact, only have 5 TM domains.

I thought Strotmann et al. (2011) wrote a decent (and not too dated) review on GPCRs, which is worth a read.

Ji TH, Grossmann M, Ji I (1998) G protein-coupled receptors. I. Diversity of receptor-ligand interactions. J Biol Chem 273(28):17299-17302.

Ling K, Wang P, Zhao J, Wu Y, Cheng Z, Wu G, Hu W, Ma L, Pei G (1999) Five-transmembrane domains appear sufficient for a G protein-coupled receptor: Functional five-transmembrane domain chemokine receptors. Proc Natl Acad Sci USA 96(14):7922-7927.

Strotmann R, Schröck K, Böselt I, Stäubert C, Russ A, Schöneberg T (2011) Evolution of GPCR: change and continuity. Mol Cell Endocrinol 331(2):170-178.
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SmashConcept
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To add to that, asking "why" questions is not really appropriate for any discussion of evolution, so it's important to choose your wording carefully.

It's been a while, but I suppose if you imagine there were only 1 TM domain, then how hard would it be for a conformation change outside the cell to manifest in a change inside the cell? 3TM would mean there is one loop for each terminal domain to interact with and help force conformation changes to carry throughout the molecule. 5TM means there are 2 loops on each side. 7TM means there are 3.
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