![]() | Serpin is a featured article; it (or a previous version of it) has been identified as one of the best articles produced by the Wikipedia community. Even so, if you can update or improve it, please do so. | |||||||||||||||||||||
![]() | This article appeared on Wikipedia's Main Page as Today's featured article on April 2, 2016. | |||||||||||||||||||||
|
![]() | This article is rated FA-class on Wikipedia's
content assessment scale. It is of interest to the following WikiProjects: | |||||||||||||||||||||||||||||||||
|
All structural figures now added - on reflection I actually think that a TBG image would be better under a TBG page. Table reasonably well referenced Catalytic mechanism figure adapted and added as suggested. I have asked a colleague for an attractive cell biology figure to go at the top of the page More references added through out and some cleanup and wikifying performed (thanks to Arcadian and Kjaergaard) Have some ideas for additional sections - serpin folding, comment on exception to Anfinsens etc, illustrate phylogeny of superfamily, section on fly serpins and worm serpins.
Jcwhizz 09:39, 12 March 2007 (UTC)
Polymer picture - combine with delta picture (in progress) Add "disease caused by deficiency" to human serpin list Add figure illustrating key serpin regions that are often mutated in human disease (Breach, shutter). Perhaps put in figure with conserved residues highlighted (or is this too specialised?) Expand polymer section and make more general linkages with protein misfolding Illustrate non-inhibitory section with picture of TBG, ligand and binding site highlighted. General cleanup, add a few more references, PMIDs where possible. Any other suggstions? Jcwhizz 00:59, 11 March 2007 (UTC)
In my opinion, the broad content in the serpin page is now scientificaly accurate, up-to-date, reasonably concise and appropriately structured (I have to admit to some bias, however, having written some of it!). I feel that the only major omission is a picture of a model of a serpin polymer (which I am making). I think there is still quite a bit of stylistic correction and cleanup to do. Major references in the field have been added, however, secondary references should probably be added too? I think the time is right for some more general feedback from the MCB comunity, however, I'm unsure how to start the review process. Jcwhizz 09:42, 11 March 2007 (UTC)
Right now the article is very good on the structural stuff, but contains very little about other aspects about serpins. This bias is probably related to the interests of the contributors. We need a beautiful picture to place in the top of the page to catch the interest of the readers. I think we need to show the catalytic cycle of serine proteases as well, showing explicitly where it is interupted. And I think the table should have the protein names as the first column, rather than the genes, since that are the names they are primarily known by... Kjaergaard 10:17, 11 March 2007 (UTC)
Agree with you on the structural bias (have to confess thats my area) and the catalytic cycle. However, there is a huge effort in the serpin community to stop using the "old" serpin names (which and to use the proper nomenclature SERPINA1 etc as the protein name - I will edit the Gene name to read Protein name (which is actually correct). I'll have a think about a beautiful (non structural) picture.
210.49.179.196 11:02, 11 March 2007 (UTC)
What do you think about a really attractively stained picture of a blood clot (appropriate given the large number of serpins involved in clotting / bleeding etc) or alternatively a white blood cell (rich in serpins) - not sure where to source these though as I don't have them myself. I have to confess I thought first about a nice picture of a serpin crystal - though on reflection I realised that possibly may be too structural...:) ?
Jcwhizz 11:29, 11 March 2007 (UTC)
And I'm pretty sure that PAI-1 doesn't inhibit plasmin directly. I don't know if you have a reference claiming this... Kjaergaard 10:20, 11 March 2007 (UTC)
Will check this out
210.49.179.196 11:02, 11 March 2007 (UTC)
Yup - my mistake - fixed
Jcwhizz 11:29, 11 March 2007 (UTC)
Serpin page coming together - some major and minor things to do. Major: 1) Add more figures (polymer). 2) More extensive referencing 3) Brief two liners about the function of each human serpin - for more in depth analysis should link to relevant pages 4) Section on serpin-enzyme complex uptake by LRP-related protein receptor. 5) Section on worm serpins
Minor Add PMID ids to references that do not have them Work out how to assign a unique number to a reference (i.e. so it is not repeated in the bibliography
Jcwhizz 05:26, 7 March 2007 (UTC)
What is the basis for saying that serpins are enzymes? As I understand it they are "suicide substrates". What reaction are they supposed to catalyze? Josh Cherry 23:15, 14 Jun 2004 (UTC)
The Monday, 24 October 2005 BBC News headline,
Malaria gene 'defends mosquitoes'
http://news.bbc.co.uk/1/hi/health/4370960.stm
...turns out to refer to this paper:
An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16260729
The conclusion states that Anopheles stephensi SRPN6 is either directly or indirectly involved in the parasite-killing process, whereas Anopheles gambiae SRPN6 apparently acts further downstream on parasite clearance by promoting lysis.
(Mosquitoes with SRPN6 expression knocked out were ultra-susceptible to Plasmodium infection; steps are being taken to produce mosquitoes with a constitutively-active SPRN6 gene, to see what effect that has - immune mosquitoes in the wild would equal reduced Plasmodium transmission rates, until either the parasite or the insect evolved round it...)
Anyway, I just thought this might be germane to this article, but as this is the first time I've done anything on wikipedia, methought it better merely to mention it here so people can see what they think.
Cheers, Tommy B.
It might be more relevant to the Malaria article.... Kjaergaard 18:20, 15 April 2007 (UTC)
Thanks - have pasted it into the Talk:Malaria page, so people there can see what they thank. --Tommy B.
The lead has three functions. Firstly, the initial sentence should define the topic clearly and precisely without using too many technical terms. Secondly, the lead should introduce the topic and indicate why it is important. Thirdly, the lead should provide a brief summary of the main points in the article. The lead does an OK job of point one, but is still a bit short for points two and three. Aim for about three paragraphs? Tim Vickers 17:53, 28 July 2007 (UTC)
Hi Tim - good point - have expanded as suggested. Cheers James Jcwhizz 01:43, 29 July 2007 (UTC)
This is how the article, compares against the six good article criteria:
Done Jcwhizz 00:13, 4 August 2007 (UTC)
Have gone through, made all the changes requested above, and also edited to make the article more succinct. Jcwhizz 00:13, 4 August 2007 (UTC)
Sorry - spello. Jcwhizz 00:13, 4 August 2007 (UTC)
Added the term nucleophilic to make this distinction for both serine and cysteine. Jcwhizz 00:13, 4 August 2007 (UTC)
Have replaced with functional orthology. Basically the problem is that the murine repotoire of serpins is vastly expanded with respect to human serpins. So for example, where there is one human gene for SCCA-1, there are 3-4 in the mouse. Thus it is difficult to know which one to knock out to gain an understanding of the role of the human protein. Jcwhizz 00:13, 4 August 2007 (UTC)
Yes, in certain cases, for example in Tcell killing, there may be some "leakage" of Granzymes during granzyme delivery which are most likely mopped up by serpins such as PI-9. Have changed text to clarify this. Jcwhizz 00:13, 4 August 2007 (UTC)
In this instance I think it is appropriate to - within the serpin field the term co-factor is generally accepted and used to describe molecules that modulate serpin inhibitory activity. See for example, Frank Church's recent review (Rau et al., J Thromb Haemost. 2007 Jul;5 Suppl 1:102-15) - but there many other papers on this topic. Jcwhizz 00:13, 4 August 2007 (UTC)
Yes, I have to confess I have an interest :) Jcwhizz 00:13, 4 August 2007 (UTC)
Yes, good point - have shortened all legends, and moved the text of figure 4 (function of heparin) into the text. I have left the odd sentence to really emphasize key points. Jcwhizz 00:13, 4 August 2007 (UTC)
I've put this nomination on hold while the minor text changes are made. If you feel that this review is in error, feel free to take it to a
GA review. Thank you to all of the editors who worked hard to bring it to this status.
Tim Vickers
21:41, 31 July 2007 (UTC)
Thanks once again for a great and detailed review. Are you happy with the changes? Cheers James Jcwhizz 00:13, 4 August 2007 (UTC)
Thanks Tim - excellent!! - I'll have a read on what is required for nomination for FA. Cheers James Jcwhizz 22:11, 4 August 2007 (UTC)
Figure 3, "Catalytic mechanism of serine proteases" - The reaction mechanism has some problems. The nitrogen in the carboxamide kinda disappears in the last couple steps and seems to maybe be replaced with an oxygen... —Preceding unsigned comment added by 65.67.67.220 ( talk) 22:10, 8 November 2007 (UTC)
The cleaved product leaves the active site then water comes in to complete hydrolysis of the acyl enzyme intermediate. Not sure what problem you are refering to - looks like a pretty standard depiction of the reaction mechanism to me.
Jcwhizz 23:04, 9 November 2007 (UTC)
Hi - thats great!! Jcwhizz 08:37, 13 November 2007 (UTC)
I love this page. I added a short description of the uterine serpins with a link to a new page I wrote on them. I hope that is OK. If not, please delete or modify. Ufpete ( talk) 12:06, 3 December 2010 (UTC)
Article is large and slow to format. It has over 170 references. Should we split it ?
Would it be sensible to split out Table 1 (which alone has over 70 references) ?
Rod57 (
talk)
09:12, 20 April 2011 (UTC)
Hi - I would be strongly against splitting it or splitting out table 1- basically the page is designed to give a comprehensive and well referenced overview of the serpin superfamily - table 1 is valuable because it gives a quick at a glance insight into the human serpins, which are of primary interest from a medical research perspective. James Whisstock ( talk) 12:06, 13 September 2011 (UTC)
In response to a previous question by Jcwhizz of how to move this article to FA. Here are my suggestions (some of which I shall try to implement myself over the coming weeks).
A-sheet polymerisation model
|
---|
![]() {{
cite journal}} : CS1 maint: multiple names: authors list (
link)</ref> The A β-sheet is in red. The RCL (magenta) of the orange molecule is inserted into the bottom of the A-sheet of the white molecule.In the absence of definitive structural data, it was, therefore, postulated that serpins polymerise via a mechanism known as A-sheet polymerisation. [1] In normal function the RCL inserts into the A β-sheet to form a fourth strand. In the A-sheet polymerisation model, it was suggested that the RCL of one serpin molecule spontaneously inserted into the A-sheet of another, to form a long-chain polymer (figure 9). In effect, it was, thus, proposed that polymerization occurred as a consequence of the requirement of the serpin scaffold to accept an additional β-strand. Serpins were one of the first families for which disease-causing mutations were directly analyzed in reference to the available crystal structures. [2] In support of the A-sheet polymerisation model, it was noted that many serpin mutations that cause polymerisation localise to two distinct regions of the molecule termed the shutter and the breach. The shutter and the breach contain highly conserved residues, underlie the path of RCL insertion, and are proposed to be important for conformational change. Two structures of cleaved serpin polymers have been solved; both of which reveal RCL / A-sheet sheet linkages similar to those predicted by the A sheet polymerisation mechanism. [3] [4] However, in direct contrast to the known properties of physiological serpin polymers, crystals of cleaved serpin A-sheet polymers readily dissociate into monomeric forms. [3] [4] Events associated with serpin polymerisation occur during the folding of the molecule, and that mutations that cause serpinopathies interfere with the ability of the serpin to fold to the metastable native state. [5] In normal serpin folding, the serpin rapidly moves through a key folding intermediate to attain the native state. It is the serpin folding intermediate that has the ability to polymerise, hence it is important that this folding species rapidly moves on to adopt native state. citation needed Mutations such as the Z-antitrypsin variant (Glu 342 to Lys) somehow prevent the final stage of seprin folding and cause the accumulation of the folding intermediate. As a result, population of the folding intermediate resulted in polymer formation. [5] It was noted that once folded, the Z-antitrypsin variant closely resembles wild-type material in terms of thermal stability and inhibitory activity. [5] [6] Together, these data have presented an important challenge to the A-sheet model for serpin polymerisation. On the one hand, the idea that serpin polymer formation essentially takes advantage of the serpin mechanism of conformational change is an attractive one. On the other, the biophyiscal data in particular suggest that it is a folding intermediate (rather than the native form) that polymerises, and it is clear that this intermediate must have different structural properties to the native, folded state. It is thought that physiological serpin polymers do not form via the A-sheet mechanism, but instead form via more extensive domain swapping events. [7] References
|
With these changes, I think it'd be reasonable to submit it for FA nomination and see what the reviewers identify. Although it looks like a lot, I don't think it'll take too much to fix up these bits and pieces. T.Shafee(Evo﹠Evo) talk 11:27, 1 November 2015 (UTC)
I've managed to do most of the big changes that I identified above ( before and after changes).
The main changes have been:
I've also taken the liberty of updating some of the images. Hopefully they're clearer. T.Shafee(Evo﹠Evo) talk 05:53, 20 December 2015 (UTC)
1. When were the first serpins discovered, and when was the first structure solved?
2. Are most serpin-related diseases due to polymerisation or inactivity? From the information balance in the article, currently it looks as though pathologies due to merely inactive serpins are rare.
3. Are there any pathologies of over-active serpins?
4. Is anything known about the evolution of non-inhibitory serpins? Does the RCL have an intersting role in any of them or are they just inert storage/ carrier proteins?
5. Is there anything interesting to be said about how the high-energy stressed state is produced by the ribosome? E.g. a sentence in the Structure section.
I'll add to the above list if I think of any more things! T.Shafee(Evo﹠Evo) talk 11:08, 13 December 2015 (UTC)
Hello fellow Wikipedians,
I have just modified one external link on Serpin. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
When you have finished reviewing my changes, you may follow the instructions on the template below to fix any issues with the URLs.
This message was posted before February 2018.
After February 2018, "External links modified" talk page sections are no longer generated or monitored by InternetArchiveBot. No special action is required regarding these talk page notices, other than
regular verification using the archive tool instructions below. Editors
have permission to delete these "External links modified" talk page sections if they want to de-clutter talk pages, but see the
RfC before doing mass systematic removals. This message is updated dynamically through the template {{
source check}}
(last update: 5 June 2024).
Cheers.— InternetArchiveBot ( Report bug) 13:16, 24 September 2017 (UTC)
![]() | Serpin is a featured article; it (or a previous version of it) has been identified as one of the best articles produced by the Wikipedia community. Even so, if you can update or improve it, please do so. | |||||||||||||||||||||
![]() | This article appeared on Wikipedia's Main Page as Today's featured article on April 2, 2016. | |||||||||||||||||||||
|
![]() | This article is rated FA-class on Wikipedia's
content assessment scale. It is of interest to the following WikiProjects: | |||||||||||||||||||||||||||||||||
|
All structural figures now added - on reflection I actually think that a TBG image would be better under a TBG page. Table reasonably well referenced Catalytic mechanism figure adapted and added as suggested. I have asked a colleague for an attractive cell biology figure to go at the top of the page More references added through out and some cleanup and wikifying performed (thanks to Arcadian and Kjaergaard) Have some ideas for additional sections - serpin folding, comment on exception to Anfinsens etc, illustrate phylogeny of superfamily, section on fly serpins and worm serpins.
Jcwhizz 09:39, 12 March 2007 (UTC)
Polymer picture - combine with delta picture (in progress) Add "disease caused by deficiency" to human serpin list Add figure illustrating key serpin regions that are often mutated in human disease (Breach, shutter). Perhaps put in figure with conserved residues highlighted (or is this too specialised?) Expand polymer section and make more general linkages with protein misfolding Illustrate non-inhibitory section with picture of TBG, ligand and binding site highlighted. General cleanup, add a few more references, PMIDs where possible. Any other suggstions? Jcwhizz 00:59, 11 March 2007 (UTC)
In my opinion, the broad content in the serpin page is now scientificaly accurate, up-to-date, reasonably concise and appropriately structured (I have to admit to some bias, however, having written some of it!). I feel that the only major omission is a picture of a model of a serpin polymer (which I am making). I think there is still quite a bit of stylistic correction and cleanup to do. Major references in the field have been added, however, secondary references should probably be added too? I think the time is right for some more general feedback from the MCB comunity, however, I'm unsure how to start the review process. Jcwhizz 09:42, 11 March 2007 (UTC)
Right now the article is very good on the structural stuff, but contains very little about other aspects about serpins. This bias is probably related to the interests of the contributors. We need a beautiful picture to place in the top of the page to catch the interest of the readers. I think we need to show the catalytic cycle of serine proteases as well, showing explicitly where it is interupted. And I think the table should have the protein names as the first column, rather than the genes, since that are the names they are primarily known by... Kjaergaard 10:17, 11 March 2007 (UTC)
Agree with you on the structural bias (have to confess thats my area) and the catalytic cycle. However, there is a huge effort in the serpin community to stop using the "old" serpin names (which and to use the proper nomenclature SERPINA1 etc as the protein name - I will edit the Gene name to read Protein name (which is actually correct). I'll have a think about a beautiful (non structural) picture.
210.49.179.196 11:02, 11 March 2007 (UTC)
What do you think about a really attractively stained picture of a blood clot (appropriate given the large number of serpins involved in clotting / bleeding etc) or alternatively a white blood cell (rich in serpins) - not sure where to source these though as I don't have them myself. I have to confess I thought first about a nice picture of a serpin crystal - though on reflection I realised that possibly may be too structural...:) ?
Jcwhizz 11:29, 11 March 2007 (UTC)
And I'm pretty sure that PAI-1 doesn't inhibit plasmin directly. I don't know if you have a reference claiming this... Kjaergaard 10:20, 11 March 2007 (UTC)
Will check this out
210.49.179.196 11:02, 11 March 2007 (UTC)
Yup - my mistake - fixed
Jcwhizz 11:29, 11 March 2007 (UTC)
Serpin page coming together - some major and minor things to do. Major: 1) Add more figures (polymer). 2) More extensive referencing 3) Brief two liners about the function of each human serpin - for more in depth analysis should link to relevant pages 4) Section on serpin-enzyme complex uptake by LRP-related protein receptor. 5) Section on worm serpins
Minor Add PMID ids to references that do not have them Work out how to assign a unique number to a reference (i.e. so it is not repeated in the bibliography
Jcwhizz 05:26, 7 March 2007 (UTC)
What is the basis for saying that serpins are enzymes? As I understand it they are "suicide substrates". What reaction are they supposed to catalyze? Josh Cherry 23:15, 14 Jun 2004 (UTC)
The Monday, 24 October 2005 BBC News headline,
Malaria gene 'defends mosquitoes'
http://news.bbc.co.uk/1/hi/health/4370960.stm
...turns out to refer to this paper:
An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16260729
The conclusion states that Anopheles stephensi SRPN6 is either directly or indirectly involved in the parasite-killing process, whereas Anopheles gambiae SRPN6 apparently acts further downstream on parasite clearance by promoting lysis.
(Mosquitoes with SRPN6 expression knocked out were ultra-susceptible to Plasmodium infection; steps are being taken to produce mosquitoes with a constitutively-active SPRN6 gene, to see what effect that has - immune mosquitoes in the wild would equal reduced Plasmodium transmission rates, until either the parasite or the insect evolved round it...)
Anyway, I just thought this might be germane to this article, but as this is the first time I've done anything on wikipedia, methought it better merely to mention it here so people can see what they think.
Cheers, Tommy B.
It might be more relevant to the Malaria article.... Kjaergaard 18:20, 15 April 2007 (UTC)
Thanks - have pasted it into the Talk:Malaria page, so people there can see what they thank. --Tommy B.
The lead has three functions. Firstly, the initial sentence should define the topic clearly and precisely without using too many technical terms. Secondly, the lead should introduce the topic and indicate why it is important. Thirdly, the lead should provide a brief summary of the main points in the article. The lead does an OK job of point one, but is still a bit short for points two and three. Aim for about three paragraphs? Tim Vickers 17:53, 28 July 2007 (UTC)
Hi Tim - good point - have expanded as suggested. Cheers James Jcwhizz 01:43, 29 July 2007 (UTC)
This is how the article, compares against the six good article criteria:
Done Jcwhizz 00:13, 4 August 2007 (UTC)
Have gone through, made all the changes requested above, and also edited to make the article more succinct. Jcwhizz 00:13, 4 August 2007 (UTC)
Sorry - spello. Jcwhizz 00:13, 4 August 2007 (UTC)
Added the term nucleophilic to make this distinction for both serine and cysteine. Jcwhizz 00:13, 4 August 2007 (UTC)
Have replaced with functional orthology. Basically the problem is that the murine repotoire of serpins is vastly expanded with respect to human serpins. So for example, where there is one human gene for SCCA-1, there are 3-4 in the mouse. Thus it is difficult to know which one to knock out to gain an understanding of the role of the human protein. Jcwhizz 00:13, 4 August 2007 (UTC)
Yes, in certain cases, for example in Tcell killing, there may be some "leakage" of Granzymes during granzyme delivery which are most likely mopped up by serpins such as PI-9. Have changed text to clarify this. Jcwhizz 00:13, 4 August 2007 (UTC)
In this instance I think it is appropriate to - within the serpin field the term co-factor is generally accepted and used to describe molecules that modulate serpin inhibitory activity. See for example, Frank Church's recent review (Rau et al., J Thromb Haemost. 2007 Jul;5 Suppl 1:102-15) - but there many other papers on this topic. Jcwhizz 00:13, 4 August 2007 (UTC)
Yes, I have to confess I have an interest :) Jcwhizz 00:13, 4 August 2007 (UTC)
Yes, good point - have shortened all legends, and moved the text of figure 4 (function of heparin) into the text. I have left the odd sentence to really emphasize key points. Jcwhizz 00:13, 4 August 2007 (UTC)
I've put this nomination on hold while the minor text changes are made. If you feel that this review is in error, feel free to take it to a
GA review. Thank you to all of the editors who worked hard to bring it to this status.
Tim Vickers
21:41, 31 July 2007 (UTC)
Thanks once again for a great and detailed review. Are you happy with the changes? Cheers James Jcwhizz 00:13, 4 August 2007 (UTC)
Thanks Tim - excellent!! - I'll have a read on what is required for nomination for FA. Cheers James Jcwhizz 22:11, 4 August 2007 (UTC)
Figure 3, "Catalytic mechanism of serine proteases" - The reaction mechanism has some problems. The nitrogen in the carboxamide kinda disappears in the last couple steps and seems to maybe be replaced with an oxygen... —Preceding unsigned comment added by 65.67.67.220 ( talk) 22:10, 8 November 2007 (UTC)
The cleaved product leaves the active site then water comes in to complete hydrolysis of the acyl enzyme intermediate. Not sure what problem you are refering to - looks like a pretty standard depiction of the reaction mechanism to me.
Jcwhizz 23:04, 9 November 2007 (UTC)
Hi - thats great!! Jcwhizz 08:37, 13 November 2007 (UTC)
I love this page. I added a short description of the uterine serpins with a link to a new page I wrote on them. I hope that is OK. If not, please delete or modify. Ufpete ( talk) 12:06, 3 December 2010 (UTC)
Article is large and slow to format. It has over 170 references. Should we split it ?
Would it be sensible to split out Table 1 (which alone has over 70 references) ?
Rod57 (
talk)
09:12, 20 April 2011 (UTC)
Hi - I would be strongly against splitting it or splitting out table 1- basically the page is designed to give a comprehensive and well referenced overview of the serpin superfamily - table 1 is valuable because it gives a quick at a glance insight into the human serpins, which are of primary interest from a medical research perspective. James Whisstock ( talk) 12:06, 13 September 2011 (UTC)
In response to a previous question by Jcwhizz of how to move this article to FA. Here are my suggestions (some of which I shall try to implement myself over the coming weeks).
A-sheet polymerisation model
|
---|
![]() {{
cite journal}} : CS1 maint: multiple names: authors list (
link)</ref> The A β-sheet is in red. The RCL (magenta) of the orange molecule is inserted into the bottom of the A-sheet of the white molecule.In the absence of definitive structural data, it was, therefore, postulated that serpins polymerise via a mechanism known as A-sheet polymerisation. [1] In normal function the RCL inserts into the A β-sheet to form a fourth strand. In the A-sheet polymerisation model, it was suggested that the RCL of one serpin molecule spontaneously inserted into the A-sheet of another, to form a long-chain polymer (figure 9). In effect, it was, thus, proposed that polymerization occurred as a consequence of the requirement of the serpin scaffold to accept an additional β-strand. Serpins were one of the first families for which disease-causing mutations were directly analyzed in reference to the available crystal structures. [2] In support of the A-sheet polymerisation model, it was noted that many serpin mutations that cause polymerisation localise to two distinct regions of the molecule termed the shutter and the breach. The shutter and the breach contain highly conserved residues, underlie the path of RCL insertion, and are proposed to be important for conformational change. Two structures of cleaved serpin polymers have been solved; both of which reveal RCL / A-sheet sheet linkages similar to those predicted by the A sheet polymerisation mechanism. [3] [4] However, in direct contrast to the known properties of physiological serpin polymers, crystals of cleaved serpin A-sheet polymers readily dissociate into monomeric forms. [3] [4] Events associated with serpin polymerisation occur during the folding of the molecule, and that mutations that cause serpinopathies interfere with the ability of the serpin to fold to the metastable native state. [5] In normal serpin folding, the serpin rapidly moves through a key folding intermediate to attain the native state. It is the serpin folding intermediate that has the ability to polymerise, hence it is important that this folding species rapidly moves on to adopt native state. citation needed Mutations such as the Z-antitrypsin variant (Glu 342 to Lys) somehow prevent the final stage of seprin folding and cause the accumulation of the folding intermediate. As a result, population of the folding intermediate resulted in polymer formation. [5] It was noted that once folded, the Z-antitrypsin variant closely resembles wild-type material in terms of thermal stability and inhibitory activity. [5] [6] Together, these data have presented an important challenge to the A-sheet model for serpin polymerisation. On the one hand, the idea that serpin polymer formation essentially takes advantage of the serpin mechanism of conformational change is an attractive one. On the other, the biophyiscal data in particular suggest that it is a folding intermediate (rather than the native form) that polymerises, and it is clear that this intermediate must have different structural properties to the native, folded state. It is thought that physiological serpin polymers do not form via the A-sheet mechanism, but instead form via more extensive domain swapping events. [7] References
|
With these changes, I think it'd be reasonable to submit it for FA nomination and see what the reviewers identify. Although it looks like a lot, I don't think it'll take too much to fix up these bits and pieces. T.Shafee(Evo﹠Evo) talk 11:27, 1 November 2015 (UTC)
I've managed to do most of the big changes that I identified above ( before and after changes).
The main changes have been:
I've also taken the liberty of updating some of the images. Hopefully they're clearer. T.Shafee(Evo﹠Evo) talk 05:53, 20 December 2015 (UTC)
1. When were the first serpins discovered, and when was the first structure solved?
2. Are most serpin-related diseases due to polymerisation or inactivity? From the information balance in the article, currently it looks as though pathologies due to merely inactive serpins are rare.
3. Are there any pathologies of over-active serpins?
4. Is anything known about the evolution of non-inhibitory serpins? Does the RCL have an intersting role in any of them or are they just inert storage/ carrier proteins?
5. Is there anything interesting to be said about how the high-energy stressed state is produced by the ribosome? E.g. a sentence in the Structure section.
I'll add to the above list if I think of any more things! T.Shafee(Evo﹠Evo) talk 11:08, 13 December 2015 (UTC)
Hello fellow Wikipedians,
I have just modified one external link on Serpin. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
When you have finished reviewing my changes, you may follow the instructions on the template below to fix any issues with the URLs.
This message was posted before February 2018.
After February 2018, "External links modified" talk page sections are no longer generated or monitored by InternetArchiveBot. No special action is required regarding these talk page notices, other than
regular verification using the archive tool instructions below. Editors
have permission to delete these "External links modified" talk page sections if they want to de-clutter talk pages, but see the
RfC before doing mass systematic removals. This message is updated dynamically through the template {{
source check}}
(last update: 5 June 2024).
Cheers.— InternetArchiveBot ( Report bug) 13:16, 24 September 2017 (UTC)