Talk:Proteasome

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This article was the MCB Collaboration of the Month for the month of November 2006. For more details, see the MCB Collaboration of the Month history.

Although the proteasome article does include information regarding the ubiquitin proteasome system, it is important to recognize that the proteasome is only the final component of the ubiquitin proteasome system. The ubiquitin proteasome system is extremely extensive and has a high relevance to many areas of biomedical science e.g. cancer. Therefore I believe it is justified for this article exist in it's own right, but in a much more extensive form than at present.

The above paragraph was copied from the article The Ubiquitin Proteasome System which was merged with this Proeasome article. --Splette ^Talk 10:22, 19 October 2006 (UTC)

Contents 1 Bortezomib 2 Pathway diagram 3 Consider for GA 4 Lower level? Schematic diagram? 5 Proteasome category question 6 Ubiquitin proteasome pathway

[edit] Bortezomib

Pharmacological information should relate primarily to bortezomib, the proteasome inhibitor used for multiple myeloma. JFW | T@lk 12:32, 1 November 2006 (UTC)

[edit] Pathway diagram

Motivated by the impressive diagrams of WikipedianProlific I'd like to have a go, too and draw one for the ubiquitin-proteasome-pathway. What steps do you think we should include (maybe starting from ubiquitination...) and do you know any good reviews about the topic? --Splette :) ^Talk 23:31, 2 November 2006 (UTC)

Great idea - could be useful in the ubiquitin article also. There's overview with a very schematic diagram in this paper on the role of the proteasome in autoimmune disease, and a thorough but slightly unorganized review with diagrams in this paper - IMO the structural schematics with the alpha/beta/etc subunits in the second paper would be particularly nice. Opabinia regalis 07:31, 13 November 2006 (UTC)

[edit] Consider for GA

I think that this article is about ready for GA nomination... what do you all think? – ClockworkSoul 15:00, 2 December 2006 (UTC)

I've got a bit of text left to add on the immunoproteasome and its products as MHC ligands, and Splette is planning to create a diagram or two soon, so I'd rather wait just a bit. On that general subject, though, have you heard from ShaiM recently at all? I think it would be great for the project if cell nucleus went to FAC, but since he did the balance of the work on that article, I'd hate to nominate it without him. Opabinia regalis 00:57, 3 December 2006 (UTC)

[edit] Lower level? Schematic diagram?

Ummm, my initial impression is that the article is wonderfully complete; but it could be daunting for a typical lay-reader, who might benefit from a rough sketch of the structure and function early on. Maybe you agree? If I were a novice reader (not too far off ;), I think I might have an easier time reading more like this:

The proteasome is a barrel-like structure whose core consists of four stacked rings of seven protein subunits each (reference schematic diagram here). The proteins of the inner two rings (denoted as the β subunits) can act as "protein scissors", cutting a protein into short unfolded peptides, typically only 7-11 residues long; the "blades" of these scissors are found only on the inside of the barrel, however. The proteins of the outer rings (called the α subunits) control access to the inside of the barrel, forming a very narrow gateway (≈1.1 nm across) through which only unfolded proteins may pass. Thus, the proteasome identifies proteins tagged for destruction, unfolds them and threads them into the barrel, where they are chopped into small pieces.

The proteasome is one of the main mechanisms responsible for degrading cellular proteins. Inhibition or clogging of the proteasome causes unwanted proteins to accumulate in the cell, and can lead to cell death. In general, the proteasome chops indiscriminately; however, in a few cases, the proteasome makes only specific cleavages that help a protein reach its mature form. In higher organisms, many of the resulting peptides are sent to the cell surface, where they report on the proteins being synthesized within the cell; in particular, this allows the intracellular production of foreign viral proteins to be detected extracellularly, provoking the immune system to flag that whole cell for destruction.

Ubiquitin is the tag that marks proteins for destruction by the proteasome or, more properly, a long chain of ubiquitin molecules attached to a lysine of the ill-fated protein (reference another schematic diagram here)...

This is just a sketch and, since I'm going from memory, I'm not even sure whether it's accurate! It's just meant to give you an idea of the level that I think might be more comfortable for many non-expert readers. If you all think it'd be helpful, I'd be happy to make a 2D (subunits=circles) or 3D (subunits=spheres) schematic Figure of the 20S proteasome and the poly-Ub tag.

I'll look the article over later again today and see if I have any other ideas/suggestions; this was just a cursory look. Willow 16:24, 6 December 2006 (UTC)

We've talked about a schematic for the 20S particle; Splette originally was planning on creating something similar, but I think he's been rather busy lately, if you'd like to do one. I tried just coloring the subunits in one of the proteasome structures by α or β ring, but I think a schematic would be much easier to look at.

I think you're probably right that the lead jumps into specifics too soon and could use more explanation... 'protein scissors' might be going a little too far; we do link protease, after all. I did a little bit of a rewrite; take a look... I don't think it's an improvement from a writing standpoint, but maybe it's less intimidating? Opabinia regalis 02:46, 7 December 2006 (UTC)

OK, I'll try to make a decent schematic sometime today. Do you have any special preferences for colors or layout? My initial thought is to represent the proteasome by 3D spheres located at the centroid of each subunit, perhaps using the same colors as you do in the ribbon diagram? A cutaway diagram might be cool, too, say, by removing two subunits from each ring so that the reader could look inside and see the catalytic threonines — they're found in the crystal structure, I hope, not too floppy/disordered? Oooh! cooler yet, how about modeling in a hapless polypeptide in the throes of its destruction? I'll fool around and try to make a diagram that's instructive, yet respectful of the moritura.

Re:the lead section, I'm still worried that it may confound even smart lay-people, or at least make for slow reading, since they'll have to look up what "sub-unit", "complex", "protease", etc. means. Here I feel an awful pang of conscience, since Laplace-Runge-Lenz vector is far worse for obscurity. :( — BTW, thanks very much for your excellent insights/comments over there; it's so helpful to have an extra five non-physicist/mathematician eyes look it over! :) — Still, although my own articles fall short, I would warmly encourage you to make the lead section even more accessible to those smart lay-people who may not know the terminology but wish to form a picture of the proteasome, what it's doing, and why. I sometimes think of a much-cherished aunt, but you could imagine writing for a fondly remembered history professor, a hip high-school physics teacher, a nice doctor, a savvy science reporter, or, say, a judge deciding a patent case involving proteasomes. Willow 12:16, 7 December 2006 (UTC)

I reorganized the structure paragraph a bit in the hopes of being a bit clearer. (though I think those who need to look up 'subunit' might have bigger problems... :) I think my original idea might have been the right way to go after all - the existing proteasome image is excellent, but it might give a clearer picture and cut down on the ancillary text if the alpha and beta rings were different colors. I think the cutaway idea is great. There are many structures of proteasomes complexed with inhibitors; I don't think there's one with a polypeptide - that would probably be difficult to cocrystallize - but since the original images were so nice, I didn't look too hard for new structures. Opabinia regalis 02:42, 9 December 2006 (UTC)

Rather than locating a scanner, I thought you might appreciate a Figure or three:

• Image:1G0U_subunits_sideview.png
• Image:1G0U_subunits_topview.png
• Image:1G0U_active_sites_cutaway3.png

They're described in more detail on their respective pages on the Commons. I had lots of fun making them — the proteasome is so beautiful!

Are these Figures kind of what you wanted? The third one is cute, but might need more refinement? I can fix them up however you'd like. Dream big, for magic abounds. ;) Willow 23:52, 12 December 2006 (UTC)

Excellent! You are once again awesome :) Added the first two to the structure section; what do you think?

The proteasome is a beautiful structure, isn't it? The third image is very cool - my first thought would be to make the CA atom spheres smaller, so they don't immediately catch the eye when you look at the image. Does MOLMOL allow depth cueing/fog? It might give a better sense of the 'cutaway-ness' of the middle section. Another idea - just kind of thinking 'out loud' - would be to replace the solid green spheres with a translucent green outline of the molecular surface of the alpha subunits, to illustrate the binding interactions, but that might not mesh well with the cutaway idea.

Also, you should render the final result twice as big with antialiasing and think about nominating it as a featured picture. They need more proteins! :) Opabinia regalis 01:48, 13 December 2006 (UTC)

MOLMOL does indeed have fog depth-cueing and I succeeded in shrinking the atoms down to a more decorous 3 Å. But looking at image #3 and its successors more closely, I noticed that some of the grey "loop" ribbons seemed disconnected, which I don't understand and can't seem to fix. :( So, I'm thinking of trying to re-make the Figure in PyMOL, with which I have only the vaguest experience. (Willow hears the beating of mighty wings as she rushes in. — "What can that be?" she wonders. "It sounds familiar." ;) Can you wait until tomorrow sometime? I'll do my best. :) Willow 23:23, 13 December 2006 (UTC)

No problem waiting, I'm not doing any real work tonight :) When you did the cutaway thing, did you just remove the extra subunits, or use a clipping plane? Maybe the disconnections are near or far clipping plane mispositioning errors? But you probably thought of that already anyway. Opabinia regalis 05:58, 14 December 2006 (UTC)

[edit] Proteasome category question

copied from User_talk:Serephine

Is it really an organelle? I don't think of it that way, and the closest text I had on hand gives it the next classification down - "molecular machine" - which is not really specific enough to get its own category. Opabinia regalis 03:31, 19 December 2006 (UTC)

I wasn't totally sure myself, however, I checked with a Google search ([1] [2] [3]) and found the scientific community to largely refer to it as an organelle in addition to machinery. I couldn't find anything disputing its inclusion as an organelle. Also, it is consistent with the definition of an organelle: In cell biology, an organelle is a discrete structure of a cell having specialized functions. -- Serephine ♠ talk - 03:43, 19 December 2006 (UTC)

I suppose they can be organelles :) It just sounds wrong to my mind though - like calling the spliceosome an organelle (nobody's tried to do that yet, have they?). Opabinia regalis 07:00, 19 December 2006 (UTC)

Heh heh you've caught me in a categorising mood so maybe I'll try ;) If it makes you feel any better, things like centrioles and ribosomes are included as organelles even though they have similarly non-membranous structures. -- Serephine ♠ talk - 07:21, 19 December 2006 (UTC)

Centrioles? Ugh. Organelles are membrane-bound, dammit :) Opabinia regalis 01:59, 20 December 2006 (UTC)

[edit] Ubiquitin proteasome pathway

Should "ubiquitin proteasome pathway" be hyphenated (i.e., ubiquitin-proteasome pathway)? A quick Google search suggests so; I have also frequently seen it hyphenated in Portuguese. Fvasconcellos 15:04, 3 January 2007 (UTC)

Missed this yesterday, but I think you're right. Also made ubiquitin-proteasome system et al. as redirects. Opabinia regalis 01:32, 5 January 2007 (UTC)

Thank you. Fvasconcellos 17:39, 5 January 2007 (UTC)