protein folding

[gocentral]

new GO term, “chaperonin-mediated protein folding”. It would be a child of GO:0006457“protein folding” and a parent of GO:0007022 “chaperonin-mediated tubulin folding”. Definition: Partial or complete folding of a nascent polypeptide, mediated by cytosolic chaperonin CCT

new GO term, “chaperonin-mediated actin folding”, is needed. It would be a sib of GO:0007022 “chaperonin-mediated tubulin folding” and child of GO:new “chaperonin-mediated protein folding”. Definition: Folding of actin into a native monomer, mediated by cytosolic chaperonin CCT

The draft Reactome pathway "Protein folding" http://brie8.cshl.edu/cgi-bin/eventbrowser?DB=gk\_central&ID=391251& includes discussion of these processes and cites to primary publications.

Thanks.

Peter

Reported by: deustp01

Original Ticket: "geneontology/ontology-requests/5882":https://sourceforge.net/p/geneontology/ontology-requests/5882

[gocentral]

I've asked Rama to comment, since she's GO's resident expert on protein folding (I didn't see anything amiss with the suggested terms; I just want a more informed opinion before I act on it).

m

Original comment by: mah11

[gocentral]

I really dislike the idea of having specific terms for the folding of specific proteins. A large fraction of the proteome requires or uses chaperones for folding under some set of conditions. This would lead to yet another explosion of the size of GO if implemented consistently (the other being my objections to overspecified binding terms)

Is it inappropriate to use with?

Original comment by: jimhu

[gocentral]

As Jim says, there is indeed an explosion of protein-specific process terms implied by this request although both tubulin and actin refer to families.

Maybe a better request, then would be to get the new term “chaperonin-mediated protein folding” and to make the current term GO:0007022 “chaperonin-mediated tubulin folding” obsolete with the new term as a suggested replacement, free of unwanted protein-specific features.

That works fine for us, but others who have already used GO:0007022 may disagree.

Peter

Original comment by: deustp01

[gocentral]

As Jim says, there is indeed an explosion of protein-specific process terms implied by this request although both tubulin and actin refer to families.

Maybe a better request, then would be to get the new term “chaperonin-mediated protein folding” and to make the current term GO:0007022 “chaperonin-mediated tubulin folding” obsolete with the new term as a suggested replacement, free of unwanted protein-specific features.

That works fine for us, but others who have already used GO:0007022 may disagree.

Peter

Original comment by: deustp01

[gocentral]

As Jim says, there is indeed an explosion of protein-specific process terms implied by this request although both tubulin and actin refer to families.

Maybe a better request, then would be to get the new term “chaperonin-mediated protein folding” and to make the current term GO:0007022 “chaperonin-mediated tubulin folding” obsolete with the new term as a suggested replacement, free of unwanted protein-specific features.

That works fine for us, but others who have already used GO:0007022 may disagree.

Peter

Original comment by: deustp01

[gocentral]

As Jim says, there is indeed an explosion of protein-specific process terms implied by this request although both tubulin and actin refer to families.

Maybe a better request, then would be to get the new term “chaperonin-mediated protein folding” and to make the current term GO:0007022 “chaperonin-mediated tubulin folding” obsolete with the new term as a suggested replacement, free of unwanted protein-specific features.

That works fine for us, but others who have already used GO:0007022 may disagree.

Peter

Original comment by: deustp01

[gocentral]

I'd still like to hear from Rama before we take any action, in case there are any features of the folding process that are unique to tubulins -- that's the situation in which we would add or keep terms that specifically mention a class or family of gene products.

If there are no such distinguishing features, we have a couple of options: we could broaden the name and definition of GO:0007022 such that it's no longer tubulin-specific, or make it obsolete and issue a new ID for a less specific term. There are only 5 gene products annotated to GO:0007022, so I have no preference. I presume we would want to give the same consideration to these terms as well:

alpha-tubulin folding GO:0007024 (7 gene products) beta-tubulin folding GO:0007025 (11gps) post-chaperonin tubulin folding pathway GO:0007023 (18 gps)

For gene products that don't merit specific terms, you can use "column 16" (not the "with" column, which is for supporting data that supplements the evidence code) to capture the specific information.

m

Original comment by: mah11

[gocentral]

Small point - if this is a discussion about how / whether to subdivide chaperonin-mediated folding, post-chaperonin tubulin folding pathway GO:0007023 is out of scope.

Original comment by: deustp01

[gocentral]

>For gene products that don't merit specific terms, you can use "column 16" >(not the "with" column, which is for supporting data that supplements the >evidence code) to capture the specific information.

I wanted to add my agreement to Midori's suggestion above on the use of column 16.

Original comment by: tberardini

[gocentral]

Hi,

Here are my thoughts. I am very open to discussion/suggestions.

1) Arent't all protein folding processes chaperone-mediated? BTW, the word 'chaperonin' is used to refer to ring shaped chaperone molecules like the GroEL/ES, TriC etc. So, i wouldn't add the chaperonin-mediated protein folding term.

2) GroEL/ES, TriC etc are some chaperonins. Some chaperonins require a cofactor and some don't. We have specific terms for these two processes. For example, if GroEL/ES is involved, it is cofactor dependent process, where GroES is the cofactor and TriC/CCT complexes are cofactor independent.

3) having said that, i think we can obsolete Tubulin folding terms (I will read more and confirm though). Sorry for overlooking those. CCT is involved in the folding tubulin as well and this should be captured by chaperone cofactor-independent protein folding (GO:51086). We shouldn't be creating the chaperonin-mediated actin folding term. I am reading more on CofactorA,B etc (gps involved in tubulin folding). They are all covered by protein complex assembly, protein oligomerization type terms. I will make a proposal on that next week. Sorry for the delay.

Rama

Original comment by: rbalakri

[gocentral]

"1) Arent't all protein folding processes chaperone-mediated?"

There are also proteins like ribonuclease that fold spontaneously and that need to be distinguished from the ones that need help. As far as I know, the number of proteins that fold without help is fairly large, and the lack of help does not mean that folding does not have a mechanism or follow a pathway, so it still qualifies as a biological process.

The protein-folding for which we need a term is mediated by a ring-shaped, CCT chaperonin.

Peter

Original comment by: deustp01

[gocentral]

Hi Peter,

True, many, many proteins fold spontaneously (and the process of spontaneous folding is very hard to understand from a mechanism point of view). In those cases what is the gp that needs the annotation and what is the process that you want to annotate to ? RNase is involved in self-folding? It folds because of entropy and that "self folding" is not its biological role in the cell. So i think there is no need to differentiate this case.

But may be I am not following your argument.

In any case, the term you are looking for to annotate the role of CCT/TriC is -chaperone cofactor independent protein folding, which is there in the ontology. I will think about clarifying parts of this ontology soon.

Thanks,

Rama

Original comment by: rbalakri

[gocentral]

The last sentence in Rama's second comment is the answer, as we've already figured out that additional tubulin- or actin- or whatever-specific terms are a bad idea.

My requested new GO term, “chaperonin-mediated protein folding” is already there as GO:0051085 "chaperone cofactor-dependent protein folding"

Its sibling, GO:0051086 "chaperone cofactor-independent protein folding" is there, in case we ever need to talk about ribonuclease folding as a process (not high on our agenda) but also for things like the formation of alpha/beta tubulin dimers.

Conclusion: no new terms needed; this item can be closed.

Thanks, all.

Peter

Original comment by: deustp01

[gocentral]

Thanks for all the comments.

Peter - glad you've found a term you can use.

Rama - it might be simplest to merge the tubulin-specific terms into their parents, and convert te names to narrow synonyms. But if you prefer to make them obsolete, that would be OK too.

m

Original comment by: mah11

[gocentral]

Peter,

I would like to clarify one point about the use of GO:0051086. This term is not meant for annotating proteins that self-fold correctly. There is no gp involved in such self-folding process. The protein of interest folds on its own. 51086 is meant for chaperones that operate without the need for cofactor. The word 'independent' goes with the 'cofactor' not with the 'chaperone'. So, GroEL/ES complex will be annotated to chaperone cofactor-dependent protein folding and TriC will be chaperone cofactor-independent folding.

Rama

Original comment by: rbalakri

[gocentral]

Hi,

Thinking more about the two cofactor related terms, I think rewording the term name might help. How about- chaperone mediated protein folding requiring cofactor (GO:0051085) chaperone mediated protein folding independent of cofactor (GO:0051086)

Rama

Original comment by: rbalakri

[gocentral]

Sure. That makes sense.

Peter

Original comment by: deustp01

[gocentral]

I've renamed GO:0051085 annd GO:0051086 as Rama suggested, keeping the old names as exact synonyms. I also merged three tubulin-specific terms with the 'protein folding' parent, making the names narrow synonyms:

alpha-tubulin folding GO:0007024 beta-tubulin folding GO:0007025 chaperonin-mediated tubulin folding GO:0007022

I haven't merged the last term that mentions tubulin because the discussion didn't touch on it as much.

Original comment by: mah11

[gocentral]

• assigned_to: nobody --> gomidori
• status: open --> closed-works-for-me

Original comment by: mah11