Talk:G protein-coupled receptor

	This article is within the scope of WikiProject Molecular Biology, a collaborative effort to improve the coverage of Molecular Biology on Wikipedia. If you would like to participate, please visit the project page, where you can join the discussion and see a list of open tasks.Molecular BiologyWikipedia:WikiProject Molecular BiologyTemplate:WikiProject Molecular BiologyMolecular Biology articles
???	This article has not yet received a rating on the importance scale.
	This article is supported by the Molecular and Cell Biology task force (assessed as Mid-importance).
	This article is within the scope of the Cell Signaling task force, a task force which is currently considered to be inactive.

Neuroscience Mid‑importance

	This article is within the scope of WikiProject Neuroscience, a collaborative effort to improve the coverage of Neuroscience on Wikipedia. If you would like to participate, please visit the project page, where you can join the discussion and see a list of open tasks.NeuroscienceWikipedia:WikiProject NeuroscienceTemplate:WikiProject Neuroscienceneuroscience articles
Mid	This article has been rated as Mid-importance on the project's importance scale.

Biophysics (inactive)

This article is within the scope of WikiProject Biophysics, a project which is currently considered to be inactive.BiophysicsWikipedia:WikiProject BiophysicsTemplate:WikiProject BiophysicsBiophysics articles

Signal transduction

"The transduction of the signal through the membrane by the receptor is not completely understood. It is known that the inactive G protein is bound to the receptor in its inactive state. Once the ligand is recognized, the receptor shifts conformation and thus mechanically activates the G protein, which detatches from the receptor. The receptor can now either activate another G protein, or switch back to its inactive state. "

This is actually rather at odds with the current idea of GPCR activation.

The results of many hybrid and mutant receptor experiments, as well as evidence of agonist trafficking and constituitive activation, suggest a model of conformational selection rather than the conformational alteration described above (which is basically the same as the lock-and-key hypothesis of enzyme activation).

Current thinking is generally based around the Extended Ternary Complex Model (ETCM). In this model the GPCR and the G-protein exist in a continuum of states which can all occur in the absence of a ligand. Some of these states are active, some inactive. Some have the G-protein bound to the receptor, some do not.

Unfortunately this is difficult to express without a diagram. I'll post one here when I have time to find one.

The idea is basically that the GPCR and the G-protein continually fluctuate between active and inactive, bound and unbound states, very very quickly.

The majority of a receptor/G-protein population will (in the absence of ligands) be in inactive states, with a few being in active states. The addition of an agonist to this equilibrium shifts it in favour of the active, G-protein bound form of the receptor, which in turn creates conditions favourable for the active form of the G-protein. In other words an agonist binds very well to the active, G-protein bound form of the receptor and stabilises it (without an agonist this form has a very short half-life and is therefore only represented in a very small number of receptors in a population), giving time for the G-protein to be activated. Thus, rather than passively sitting there waiting for an agonist molecule to come along, the components of the signalling pathway are in a state of constant flux.

This model is necessary to explain the two phenomena mentioned above:

1) Agonist trafficking.

This name is given to the observed phenomenon that the same receptor can often activate different G-proteins in response to different agonists. Thus different effects can be mediated by different agonists via the same receptor.

2) Constituitive activation.

This is the situation in which GPCRs stimulate a response in the absence of any agonist. A good example of this is the GABA-B receptor. These receptors are active without the ligand (gamma-amino butyric acid, GABA) and considerably less active when it is introduced. The term which was coined for this behaviour is inverse agonism.

The model originally described makes it difficult to account for these phenomena - if the inactive receptor and G-protein are always bound then in a situation where a selection of G-proteins is available a full response to each of the various agonists trafficked by the receptor in question would not be possible (unless we posit further mechanisms in which an agonist can force the GPCR to detach from its current G-protein). Obviously if activation of the G-protein is dependent entirely upon ligand binding then constituitive activation would not be possible. — Preceding unsigned comment added by 129.11.110.216 (talk) 16:04, 15 January 2003 (UTC)[reply]

Receptor page

Receptor (proteomics) now contains a list of receptors. Please list any pages you know on that list, because it's presently a bit messy. JFW | T@lk 20:22, 14 Apr 2004 (UTC)

Pictures needed

It would really help if there were some pictures on this page...--Dan 01:53, 21 January 2006 (UTC)[reply]

We need to get some structural detail with the alpha,beta, and gamma subunits on here. More detail on strucural rearrangements caused by GDP-GTP exchange. Does anyone know if you can use swissmol and Jmol as fair use for a picture upload of a GPCR?

Thanks for adding the image, however we need to label the subunits. Well done though. (Sterichinderance 07:04, 28 April 2006 (UTC))[reply]

Move

This should be moved to G protein-coupled receptor as the proteins to which these receptors are linked are called "G proteins", not "G-proteins" (note the hyphen). As the move would require the fixing of more double redirects than I can presently manage alone, I'll just leave this note here. --David Iberri (talk) 23:21, 29 April 2006 (UTC)[reply]

I tend to agree. Please consider listing at Wikipedia:Requested moves, which is meant for such non-trivial moves. User:Ceyockey (talk to me) 03:44, 30 April 2006 (UTC)[reply]
- I lost track of this for a while, but had a few extra minutes to do the page move myself. --David Iberri (talk) 17:40, 19 May 2006 (UTC)[reply]

Structure

Should there not be mention of alpha, beta and gamma subunits, mention also of the G_s, G_i and G_q types? --Copperman 08:29, 29 May 2006 (UTC)[reply]

That's the G protein, not the GPCR --130.88.96.66 (talk) 02:00, 10 December 2007 (UTC)[reply]

Contradict

On the 7TM receptor it says that GPCRs are an important class of 7TM receptor. But here on the GPCR page, it says that 7TM receptor is a synonym for GPCR. Zargulon 10:25, 3 July 2006 (UTC)[reply]

I suppose the 7TM Receptor article is the one in a question, not the 7TM receptor one. The second one serves as redirect to the G protein-coupled receptor article itself. (I would just boldly move the redirect to the 7TM Receptor name instead that G protein-coupled receptor, but I want to clarify the reason of confusion for those, who didn't find the target. --Reo ^ON | +++ 13:35, 10 July 2006 (UTC)[reply]

I am not aware of any non G protein-coupled 7TM receptor, so I made 7TM receptor and 7TM Receptor into redirects to G protein-coupled receptor. Cacycle 03:09, 11 July 2006 (UTC)[reply]

Look at bacteriorhodopsin as an example of a non G protein-coupled 7TM receptor. It is a photoreceptor that serves as an ion channel. — Preceding unsigned comment added by 141.214.17.5 (talk) 22:23, 21 September 2006 (UTC)[reply]

Redundant figures

There is little difference between FIG 1 and FIG2. The authors should DELETE Figure 2. — Preceding unsigned comment added by 130.199.3.130 (talk) 18:53, 11 October 2006 (UTC)[reply]

I think you mean Figure 2 and 3 are similar. Figure 2 should probably be deleted since it is too small to garner any detail from--141.214.17.5 20:33, 19 October 2006 (UTC)[reply]

Removal of info on new GPCR structure (2007)

Resolved

I am curious as to the reasoning behind this reversion edit, which removed information supported by a citation (albeit not in proper form). The reversion was accompanied by the edit summary "reverting last addition -- please propose on talk page". I was not the person who added the passage that was removed, I merely detected it on my watchlist and it caused a raised eyebrow. Thank you for the explanation. Regards --User:Ceyockey (talk to me) 11:09, 4 November 2007 (UTC)[reply]

I think the reason for reverting the edit was that the interpretation of the new structure was highly misleading. It implied that homology models of human GPCRs based on the bovine rhodopsin structure would have large errors. What is far more relevant than species differences are sequence differences (which implies structure differences). If one wants to model a human GPCR that is more closely related in sequence to rhodopsin than the adrenergic receptor, it would be far better to use the bovine rhodopsin than the human adrenergic structure. If one wants to model a GPCR (human or bovine) that is closely related in sequence to the adrenergic receptor, it would be better to use the human adrenergic structure. Finally for GPCRs which are not close in sequence to either adrenergic receptor or rhodopsin, neither experimental template is likely to lead to a good model. I have re-inserted the information about the new GPCR structure with a somewhat different, and I hope more accurate interpretation. Cheers. Boghog2 13:42, 4 November 2007 (UTC)[reply]

OK - It was mostly a matter of providing the newly published information with appropriate context and counterpoint so that it wouldn't be taken at face value. I've not yet read the manuscript myself, but I'm a bit more skeptical than most, I think, on the matter of sequence-structure relationship: structural similarity can appear in the face of sequence differences and vice versa (similar sequence, different structure) in the presence of differentiating post-translational modifications. --User:Ceyockey (talk to me) 14:04, 4 November 2007 (UTC)[reply]

Any eukaryotes genomes without G-protein-coupled receptors?

The indtroductory paragraph states that GPCRs are found only in eukaryotes, and then lists major eukaryote taxa or representatives from these known to have GPCRs (plant, animal, fungi, protists). The impression is that GPCRs are thought to be a universal feature of Eukaryota, but this is not asserted explicitly.

Does anyone know of a counter-example? i.e. a eukaryote genome apparently lacking GPCRs?

Alternatively, are there likely examples of GPCRs known from any of the more exotic branches of the eukaryote tree? —Preceding unsigned comment added by Johnfravolda (talk • contribs) 16:12, 10 July 2009 (UTC)[reply]

Phosphorylation by cAMP-dependent protein kinases

In this section it reads:

"In fact any receptor causing an increase in PKA activity will cause increased amounts of this type of desensitisation of other receptors coupled to Go (e.g., dopamine receptor D2 activation may lead to β2-adrenoceptor desensitisation of this type).[22]"

The given reference does not say this as far as I can tell, also I could find no reference to Beta-2 AR Go coupling, although Gi coupling does occur as can be seen in the reference I added two sentences earlier.Repapetilto (talk) 22:01, 22 September 2009 (UTC)[reply]

Also I realized that doesnt even make sense since D2s are Gi coupled and would decrease cAMP, so I'm just going to change D2 to D1, which at least makes sense... the reference is still bad though.Repapetilto (talk) 22:01, 22 September 2009 (UTC)[reply]

D2 does activate phosphatase pathways such as extracellular signal-regulated kinases (ERK), independent of Gi / cAMP decrease, that might very well lead to heterologous receptor phosphorylation. Please do not change receptors names arbitrarily by gut-referencing... Also, too much and too specific detail is probably not good for the article and you might want to consider to be bold and taking such parts out. Cacycle (talk) 22:17, 22 September 2009 (UTC)[reply]

I think it works as a hypothetical example though. Repapetilto (talk) 12:18, 24 September 2009 (UTC)[reply]

Plants

I removed the section about plants since it was based on the GPCR1 and 2 found by the group publishing the Science paper on the topic, the claim has been disputed by several bioinformaticists. If you search on psi-blast for these proteins you find that they belong to the LanC-like super family, not GPCR. http://www.sciencemag.org/cgi/content/abstract/318/5852/914c this discovery has been questioned in future editions of Science (the original publisher of the article) as well as other journals. Until there has been a less controversial GPCR found in plants, I believe it is proper that it is removed from this article. 99.31.87.33 (talk) 03:04, 18 October 2009 (UTC)[reply]

Right. Uniprot tells about this protein: belongs to "Golgi pH regulator (TC 1.A.38) family" [1]. Any other plant "GPCR" [2] [3]? Biophys (talk) 18:02, 22 June 2010 (UTC)[reply]

Number of drugs

I found a current article Overington JP, Al-Lazikani B, Hopkins AL (2006). "How many drug targets are there?". Nat Rev Drug Discov. 5 (12): 993–6. doi:10.1038/nrd2199. PMID 17139284. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) Have no idea how to add it. It says that GPCRs make up 26.8% of current drugs, NOT half as mentioned in the article. HELP... — Preceding unsigned comment added by 64.134.221.95 (talk) 05:32, 2 March 2010 (UTC)[reply]

Thanks for catching this. The Overington paper does seem to be more definitive than the citation supporting the "around half" estimate. Therefore I have changed the text to read "approximately 30%" and added the citation that you found. Cheers. Boghog (talk) 05:57, 2 March 2010 (UTC)[reply]

Structure-Function Section

So I made that figure while filling out a study guide for comprehensive exams then cleaned it up to put it here. The text that goes along with it came from the same place, I didnt bother referencing anything at the time but its all good, just check the facts and add references, or else I'll do it later. Im kinda of busy right now though so... if someone else wants to do it that would be cool. Any questions just ask, I dont think it should be deleted though. Also if someone knows a better image format to reduce the thumbnail blur, that should also be changed...Repapetilto (talk) 05:05, 19 June 2010 (UTC)[reply]

I added a bunch more text, it has the same problems as mentioned above. I'll see about getting around to fixing that eventually.Repapetilto (talk) 08:29, 21 June 2010 (UTC)[reply]

What diseases and drugs ?

Intro says "G protein-coupled receptors are involved in many diseases, and are also the target of approximately 30% of all modern medicinal drugs[2][3]" but article, although large, doesn't seem to list or link to the diseases or drugs. Even Fillmore[2] only says "They account for the majority of best-selling drugs and about 40% of all prescription pharmaceuticals on the market. Notable examples include Eli Lilly’s Zyprexa, Schering-Plough’s Clarinex, GlaxoSmithKline’s Zantac, and Novartis’s Zelnorm."

Should we have a short section like Physiology about the diseases that could mention or link to the relevant drugs ? Rod57 (talk) 23:54, 1 March 2011 (UTC)[reply]

The challenge is that the list of drugs targeting GPCRs and the diseases these drugs treat is very diverse. The {{G protein-coupled receptors}} navbox that it is displayed at the end of the article has links to GPCR families and individual GPCRs. Many of these article contain information about drugs and/or the conditions they treat (see for example Dopamine receptor, histamine receptor, etc.) At the same time, it wouldn't hurt to add a short list or table of few well known GPCR drugs. For example here is a list of the top selling drugs by world wide sales. Starting at the top of the list, drugs that act at GPCRs include:

Drug	Therapeutic Class	Target GPCR
Clopidogrel	Platelet aggregation inhibitor	P2Y12
Olanzapine, Quetiapine, Risperidone	Antipsychotic	Several (including the dopamine and histamine receptors)
Montelukast	Anti-asthmatic	CYSLTR1
Valsartan	Antihypertensive	AGTR1

Cheers. Boghog (talk) 06:27, 2 March 2011 (UTC)[reply]

Not all 7 transmembrane domain receptors are 7 TransMembrane Domain Receptors...

Just found this the other day: AdipoR1 and 2 are seven transmembrane domain receptors, but are unlike GPCRs, in that they dont seem to associate with G-proteins, and are orientated oppositely to GPCRs in the membrane (ie. cytoplasmic N, extracellular C)

http://www.ncbi.nlm.nih.gov/pubmed/12802337

Worth a mention? There's also another link somewhere up this talk page for other non-GPCR seven transmembrane receptors. --Soltee (talk) 22:13, 11 June 2012 (UTC)[reply]

If I understand correctly, they aren't all G-protein-coupled. If that's right, I'd say yes, sure. --Tryptofish (talk) 22:17, 11 June 2012 (UTC)[reply]

I mentioned AdipoR1 and AdipoR2 in this edit. Please feel free to modify. Boghog (talk) 03:13, 12 June 2012 (UTC)[reply]

Merger proposal

The following discussion is closed. Please do not modify it. Subsequent comments should be made in a new section. A summary of the conclusions reached follows.

The result was don't merge Heterotrimeric G protein into G protein-coupled receptor and no consensus on merging Heterotrimeric G protein into G protein.Boghog (talk) 17:11, 11 August 2012 (UTC)[reply]

The proposal is that G protein and Heterotrimeric G protein be both merged into G protein-coupled receptor.

On September 2010, there was a suggestion on Talk:G protein that G protein be merged into G protein-coupled receptor. I am not an expert in this field, so I cannot suggest the reason why these two articles should be merged. From what I see, it looks like G protein should be added as a subsection of G protein-coupled receptor.

In addition, there was a merge proposal for Heterotrimeric G protein to be merged into G protein in June 2011; however, this would mean that Heterotrimeric G protein should actually be merged into G protein-coupled receptor instead, making G protein-coupled receptor a more complete article. Should the articles G protein and Heterotrimeric G protein be merged into G protein-coupled receptor? Steel1943 (talk) 17:14, 4 August 2012 (UTC)[reply]

Oppose – GPCRs and G proteins belong to two different protein families that differ substantially in both structure and function (although the functions are inter-related). There is enough reliable sources and material to maintain both as separate articles. Boghog (talk) 18:03, 4 August 2012 (UTC)[reply]

~~Support~~ Oppose – merging Heterotrimeric G protein into G protein. Sorry, but I didn't see the second proposal. Boghog (talk) 23:56, 4 August 2012 (UTC)[reply]

On second thought, it appears that there are G proteins that are not heterotrimeric, see G_protein#Types_of_G_protein_signaling, hence I now think it would make more sense to move much of the material that is specific to the heterotrimeric G proteins from G protein to Heterotrimeric G protein. Boghog (talk) 15:55, 5 August 2012 (UTC)[reply]

To put things in perspective, there is a hierarchy of protein complexes and families and corresponding articles:

G protein (≠ G protein-coupled receptor)
- Small GTPase
- Heterotrimeric G protein
  - G alpha subunit
  - G beta-gamma complex

I agree with Boghog that G proteins and the receptor proteins that they modulate are two different things. Therefore, I oppose merging anything into G protein-coupled receptor. However, although it isn't exactly what is proposed here, I think it would be a good idea to merge Heterotrimeric G protein into G protein, per the June 2011 proposal. Those are the same thing, with the heterotrimer simply being the three-dimensional form into which the G proteins assemble during biological function. There's really no rationale that I can see for a separate article about the heterotrimer. --Tryptofish (talk) 19:03, 4 August 2012 (UTC)[reply]

In response to Boghog's further comments: oh yeah, I forgot about the small GTPases (facepalm). However, it seems to me that the heterotrimers are, nonetheless, a subset of the G proteins. But I guess if there isn't a good rationale for merging the small GTPases into the G protein article, then we don't really need to merge the heterotrimers either. I really don't feel strongly about it. In any case, the primary question here is about the receptors, and I think we agree that the receptors are completely distinct from the G proteins. --Tryptofish (talk) 21:27, 5 August 2012 (UTC)[reply]

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

Course assignment

This article is part of an assignment from Saint Louis University in Spring 2013 (see the course page for more details).

— Preceding unsigned comment added by Hakkinen2013 (talk • contribs) 03:53, 19 February 2013 (UTC)[reply]

Nomenclature: Ga i/o vs Ga i/0

This page lists the former, with a letter o, while the subunit's own page uses a 0. I suggest using a 0 for both articles.

The other article: https://en.wikipedia.org/wiki/Gi_alpha_subunit

(167.206.17.113 (talk) 15:16, 9 September 2015 (UTC))[reply]

Lede looks spammy

Since I'm new to this article, I thought I would just mention it instead of deleting the offending passages myself, but this sounds too Gee Wiz and not encyclopedic:

"G protein–coupled receptors are involved in many diseases, and are also the target of approximately 40% of all modern medicinal drugs.[4][5] Two of the United States's top five selling drugs (Hydrocodone and Lisinopril) act by targeting a G protein–coupled receptor.[6] The 2012 Nobel Prize in Chemistry was awarded to Brian Kobilka and Robert Lefkowitz for their work that was "crucial for understanding how G protein–coupled receptors function.".[7] There have been at least seven other Nobel Prizes awarded for some aspect of G protein–mediated signaling." Zyxwv99 (talk) 01:19, 8 October 2015 (UTC)[reply]

I think the fact that GPCRs are the target of a large percentage of drugs is significant snd should be mentioned in the lead. I would agree that the rest of the material that you have highlighted is not appropriate for the lead and I have moved it to an new "history and significance" section. Boghog (talk) 05:26, 8 October 2015 (UTC)[reply]

Thanks. Zyxwv99 (talk) 02:13, 9 October 2015 (UTC)[reply]

800 GPCRs?

The page contains the text: "The exact size of the GPCR superfamily is unknown, but nearly 800 different human genes (or ~ 4% of the entire protein-coding genome) have been predicted to code for them from genome sequence analysis.[10]". Although I acknowledge that larger numbers are more awe-inspiring (and are frequently cited), I don't think a conjecture should be so prominently featured on this wiki page. I don't have a suggested modification or replacement, and I don't have any scientific objections to the predictions made in this cited article. I am simply suggesting that it would be better to stick to known facts rather than 12-year-old conjectures (even if those conjectures are data and model driven). I took a look and could not find anything better for a general replacement citation for a summary of the number of GPCRs (besides perhaps this annotated 200+ conjecture: https://www.ncbi.nlm.nih.gov/pubmed/15914470 , also from 2005). — Preceding unsigned comment added by 69.254.135.248 (talk) 07:04, 22 July 2017 (UTC)[reply]

Evaluation of the article

Why you have chosen this article to evaluate?

G-Protein coupled receptors really interest me as numerous physiological processes and cellular responses are based upon GPCR interactions with various signaling molecules. Not to mention my current research focuses on GPCRs and I want to learn as much as possible. GPCRs are important because according to the article the ligands or signaling molecules that interact with the receptors are related to light-sensitivity, odors, pheromones, neurotransmitters, hormones and more, reflecting the idea that GPCRs are involved in numerous processes/actions within living organisms, particularly eukaryotes. As for my preliminary impression of the article, it appears to be well organized by initially providing an overview of what is known about GPCRs regarding its structure and role, also incorporating details regarding its history. Then moving onto more specifics related to the mechanism of function, signaling, the individual cAMP and PIP2 pathways and so on. The paper also appears to be greatly detailed providing a well-rounded overview of details and images reflecting the concepts being discussed. Additionally, the sources provided are vast and reputable, further aiding in the reliability of the information being reported within the article.

Evaluate the article

When reading the lead section, the article clearly describes the topic of discussion: GPCRs. It further goes onto briefly but accurately describing the articles major sections of discussion including ligands that interact with the GPCRs, the two distinct pathways involved within the signal transduction, the various signaling subunits involved within the process and more. However, receptor regulation is not clearly outlined within the lead section and would benefit the article if some note regarding it was made within the lead. In addition, the lead discusses applications of GPCRs as important drug targets and the applications within drug development, this is not discussed within later portions or the article in greater detail thus it would be beneficial for the readers to be provided additional details. Overall, the lead section provides enough detail to gain an overview of the article and its topics without overwhelming the reader with specific details but does lack noting an overview of GPCR regulation and includes details that are not later detailed regarding drug applications of GPCRs.

As for the content of the article, information is evenly distributed among the topics of discussion without placing too much emphasis on one compared to another. This is considering what is known and understood about each of the topics discussed, yes some sections provide more information compared to others, but this is to reflect what is known and unknown, despite this the length/details of sections do not take away from other portions of the discussion. As for the relevance of the content it is critical to understand the functions of GPCRs in addition to their structure and mechanism of function, without it GPCRs as a class of receptors will not be clearly understood, this would be a limitation to their study and the study of cellular processes/disease related. Additionally, the content related to signaling and regulation contributes to the overall understanding of GPCRs. As mentioned above, the applications of GPCRs as drug targets and drug development is something that needs to be further discussed within the article and is currently lacking. Moreover, most details within the article appear to be up-to-date utilizing sources within the 2000's and the oldest source dating back to 1987. However, there is discussion surrounding the signal transduction aspect discussed within this article that contrasts with current ideas of the transduction pathway involving a conformational selections, the author of the page should look more into this.

The tone of the article appears neutral as it doesn't focus on one point of view rather provides a wide outlook to the information and understanding regarding GPCRs. Additionally, there are no claims related to the understanding that appears heavily biased towards a particular point of view. However, the claims related to the importance of GPCRs as drug targets and their pharmaceutical applications appear underrepresented and should be provided more attention. Ultimately, the article is well written and does not take any bias towards discussing any side or detail.

When examining the sources used the links appear to work upon randomly selecting many and are readily available for viewing, and many of the ones listed supports the overall claims made within the article regarding understandings, in particular for GPCR structure/function relationships as well as mechanism of action. Additionally, the facts reported are all referenced appropriately with reliable secondary sources. And for the most part the sources are within the past 20 years, which may lend to the idea that there may be new studies on GPCRs that can contribute to this paper, despite this the sources listed do come from a diverse set of authors and publications lending to the neutral tone of the writing. Upon searching for additional sources that may contribute to this article "GPCR Signaling Regulation: The role of GRKs and Arrestins" by Vsevolod V. Gurevich and Eugenia V. Gurevich is one that may further or support the discussion regarding GPCR regulation. As for the limited discussion surrounding GPCRs as drug targets "G Protein-Coupled Receptors as Targets for Approved Drugs: How Many Targets and How Many Drugs?" by Krishna Sriram and Paul A. Insel, may provide useful details for the author of this page.

Again, the details and discussion are clearly organized, and the writing is concise, easy to read and understand. As for the images used, nothing that was used was distracting but contributed to the understanding of the topics and discussion points. While the images contribute to the readings understanding they are not as well-captioned as expected, some of the captions lack some details regarding the topic that an images is intended to reflect, for example the image captioned "G-protein-coupled receptor mechanism" the image focuses on that topic and it is understood, but readers may be confused as to what is happening in the figure, so a general overview may be helpful.

When viewing the talk-page discussions, as mentioned above there is a discussion surrounding the signal transduction mechanism where the article discusses a conformational change, but current discussions may support the idea of a conformational selection rather than a change. Other discussions surround article formatting and placement of figures/images in the article, and some related to the references used. And further discussions relate to details presented within the article that may be confusing or can be further developed for the readers’ understanding. The paper is rated as a level-5 vital article in Biology and is involved in Wiki projects for Molecular Biology / MCB, Neuroscience, and Biophysics. When reading the article, Wikipedia discusses the topic in a way that it does not command an extensive background knowledge from the reader, rather presents the information in a way that everyone can understand at a college level of education. Compared to class discussions, which may require a level of background knowledge especially knowing at least what a GPCR is, and the different words used to describe processes and applications, and how we can draw comparisons between GPCRs and other cellular processes.

Overall, the article is clearly written and concise and easy to understand and well-developed, those are its strengths. Despite this, the above-mentioned comments should be taken into consideration to improve the quality of the content and understanding. To further the discussion surrounding GPCRs, I ask what impact might mutations on GPCRs have on cellular response, i.e those that involve neurotransmitters behaving as ligands? All in all, I enjoyed reading the article and look forward to any additions/edits to the page.

Abidur.rafi24 (talk) 00:53, 5 December 2022 (UTC)[reply]

x.y amino acid residue numbering superscipt

It would be nice if someone could append info on the x.y amino acid residue numbering superscript system (e.g., Asp2.68). I sometimes see this in publications. Where I work, people speculated that "2" refers to maybe transcript ID or maybe extracellular loop number or maybe transmembrane domain. Similarly, they speculate "68" must be an amino acid position, albeit that is also ambiguous to someone who does not know the rules. IUPAC nomenclature rules does not mention such a system. Since this relates to a GPCR, could it be a GPCR specific counting system and how does it work? Where is it documented? 130.238.224.66 (talk) 10:38, 10 February 2023 (UTC)[reply]