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GPCR = G-protein coupled receptor

Gi = G inhibitory alpha subunit

Gs = G stimulatory alpha subunit

Are there structural differences between Gi and Gs subunits (secondary structure)? Or is it just categorization by effect on cAMP level? (Gi inhibits cAMP production, while Gs stimulates cAMP production)

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  • $\begingroup$ Adding some more background is recommended. A good start is to remove any unnecessary acronyms and supplying some background to what the physiological function of both these peptides is. And what effort, if any, you have put in looking up the structure of both subunits (crystallography etc). $\endgroup$ – AliceD Apr 29 '15 at 5:39
  • $\begingroup$ @AliceD. This is perfectly clear if you know GPCRs. $\endgroup$ – cagliari2005 Apr 29 '15 at 5:47
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    $\begingroup$ @cagliari2005, I know what G-prot couples Rs are, I am just trying to prevent question closure. Otherwise it'll be tagged as homework. $\endgroup$ – AliceD Apr 29 '15 at 5:55
  • $\begingroup$ Jenny, both subunits differ in amino acid sequence - so differences in primary structure are inherent. Can you elaborate what you are after exactly? Secondary and/or tertiary structure perhaps? $\endgroup$ – AliceD Apr 29 '15 at 6:00
  • $\begingroup$ This is question of how the subunits are categorized. So is it the structure of subunits or effect on cAMP? Or is there a very high correlation between the structure and effect on cAMP that they are essentially the same method of categorization? $\endgroup$ – Kenny Kim Apr 29 '15 at 6:03
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Gi and Gs have a structurally different sub unit in their alpha chain.

The receptors for PGE1 and adenosine interact with inhibitory Gi, which contains the same β and γ subunits as stimulatory Gs but a different α subunit (Giα). In response to binding of an inhibitory ligand to its receptor, the associated Gi protein releases its bound GDP and binds GTP; the active Giα · GTP complex then dissociates from Gβγ and inhibits (rather than stimulates) adenylyl cyclase.

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Both β1- and β2-adrenergic receptors are coupled to G proteins (Gs), which activate adenylyl cyclase. In contrast, α1 and α2 receptors are coupled to two other G proteins, Gq and Gi, respectively. Gi inhibits adenylyl cyclase, and Gq stimulates phospholipase C to generate IP3 and DAG as second messengers.

Also this,

A comparison of chimeric receptor 1, which interacts with Gs, and chimeric receptor 3, which interacts with Gi, shows that the G protein specificity is determined primarily by the source of the cytosol-facing loop between α helices 5 and 6. A comparison of chimeras 1 and 2 indicates that α helix 7 plays a role in determining the ligand-binding . B. Kobilka et al., 1988, Science 240:1310; W. A. Catterall, 1989, Science 243:236.

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I'd recommend reading through this: http://www.ncbi.nlm.nih.gov/books/NBK21718/

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  • $\begingroup$ So in summary, structure between 5th and 6th helix is different between Gs and Gi, and this leads to binding to adenylyl cyclase at different sites, one being stimulatory and one being inhibitory. And this means a very high correlation between structure and function. Thank you for your answer! $\endgroup$ – Kenny Kim Apr 29 '15 at 20:46

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