protein folding, protein complex assembly and chaperones

[gocentral]

First of all, some defs:

protein folding ; GO:0006457 The process of assisting in the noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure. syn: chaperone activity

protein complex assembly ; GO:0006461 The aggregation and bonding together of a set of components to form a protein complex.

chaperone activity ; GO:0003754 OBSOLETE. Assists in the correct non-covalent assembly of polypeptide-containing structures in vivo, but is not a component of these assembled structures when they are performing their normal biological function.

It seems to me that we should link the first two concepts somehow (at present they are siblings under 'protein metabolism'). Could we (or do we) have a term to encompass all the processes involved in turning a nascent polypeptide chain into the "finished product"? If protein folding can be carried out by proteins not classed as chaperones (eg. a member of a complex may assist another protein which will be in that complex in folding) then perhaps we could have 'chaperone-mediated protein folding' as a direct replacement for 'chaperone activity ; GO:0003754', as to me, the def of GO:0003754 describes involvement in a process, not a function.

Reported by: girlwithglasses

Original Ticket: "geneontology/ontology-requests/1985":https://sourceforge.net/p/geneontology/ontology-requests/1985

[gocentral]

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We may need a "chaperone mediated protein comlpex assembly" also to take care of the cases where something binds a protein to prevent it from coming out of solutin until it is assembled into whatever it is that it would normally assemble with (like the example of the ribosomal proteins that need to bind certain Imp's ).

Original comment by: hdrabkin

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I think it would be useful to have some terms to represent the processes related to protein complexes, eg:

protein complex metabolism - chemical reactions (inc. biosynth and catabolism) of a protein complex protein complex biosynthesis or assembly - making the components of the complex and putting them together protein subunit biosynthesis - biosynthesis of the protein subunits that make up the complex protein complex assembly ; GO:0006461 - putting together the subunits in the right quaternary structure

where a protein complex is defined (as in component) as "any protein group of two or more subunits, which may or may not be identical. Protein complexes may have other associated nonprotein prosthetic groups, such as nucleic acids, metal ions or carbohydrate groups."

We would then have a structure like this under metabolism:

macromolecule metabolism [i]protein complex metabolism ; GO:new1 ---[i]protein complex biosynthesis or assembly ; GO:new2 ------[i]protein complex assembly ; GO:0006461 ------[i]protein subunit biosynthesis ; GO:new3 [i]protein metabolism ---[i]protein biosynthesis ; GO:0006412 ------[i]protein subunit biosynthesis ; GO:new3 ---[i]protein folding ; GO:0006461

Is it correct to say that protein complexes get folded or is it just single polypeptides that are folded? Does folding mean generating the tertiary structure of a polypeptide or is it broader/narrower?

I would also suggest the following changes (assuming that protein folding means generating polypeptide tertiary structure):

protein folding ; GO:0006457 - The process of assisting in the noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure. clarify def: The noncovalent assembly of single chain polypeptides into the correct tertiary structure.

Add child: chaperone-mediated protein folding ; GO:NEW - The noncovalent assembly of single chain polypeptides into the correct tertiary structure, mediated by chaperone molecules, which do not form part of the finished protein.

prot complex assembly ; GO:0006461 - The aggregation and bonding together of a set of components to form a protein complex. clarify def: The aggregation and bonding together of a set of components to form a protein complex; these components include protein subunits and nonprotein prosthetic groups.

Add child: chaperone-mediated protein complex assembly ; GO:NEW - The aggregation and bonding together of a set of components to form a protein complex, mediated by chaperone molecules, which do not form part of the finished complex.

If useful, we could also add a term: protein stabilization during protein complex assembly The process by which unfolded or partially folded protein subunits are protected from degradation or structural alteration during the assembly of a protein complex.

• Harold, that might be suitable for your protein that prevents something from coming out of solution so that the protein complex can be assembled.

Original comment by: girlwithglasses

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Amelia,

I don't think we need the following terms: 1) protein complex biosynthesis/assembly- usually individual polypeptides are synthesized and are put together to form a complex. So the existing term 'protein complex assembly' is sufficient. 2) 'protein subunit biosynthesis'. A protein subunit of a complex is essentially a polypeptide chain. So it is synonymous with 'protein biosynthesis'.

I believe protein folding covers both single polypeptide and protein complexes and it is used in a broader sense. So please don't change the definition.

We don't need 'chaperone mediated protein folding' term (b'cos I believe that is an unique process and we don't need to distinguish it from anything else).

It is okay to add chaperone mediated protein complex assembly b'cos sometimes a metal ion or some cofactor can assist in assembly as opposed to a chaperone assisiting the assembly. So, it is okay to create this term.

I would also not add 'protein stabilization during protein complex assembly' because the term 'unfolded protein binding' can be used to annotate to such gene products. Most chaperones bind to unfolded protein to prevent aggregation. I would rather broaden the definition of the term 'unfolded protein binding'.

Thanks and sorry it took me so long to get back. Please let me know if you have any questions.

Rama

Original comment by: rbalakri

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The reason for adding 'protein stabilization during protein complex assembly' would be to use it as a process term to go with the function 'unfolded protein binding'. It just adds a bit of context really. If it's superfluous it can be ignored.

The protein complex terms were suggested since there is soon going to be a component term 'protein complex'. They could just be added as synonyms to existing terms instead.

Harold, would you be satisfied with the addition of 'chaperone-mediated protein complex assembly' - will that solve your 'chaperone activity' reannotations? If so, I will add the term and close this item.

Original comment by: girlwithglasses

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In the example that I cited that (the IMP9), yes, the 'chaperone-mediated proteim complex assembly' would be term that could be used. BUT, the action of chaperone activity would not just relate to the assembly of a complex, but even, perhaps to a single protein.

Original comment by: hdrabkin

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Before I add any terms, is "protein complex assembly, multichaperone pathway" supposed to represent "chaperone-mediated protein complex assembly"? It's undefined at the moment...

Original comment by: girlwithglasses

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Amelia,

1) Regarding 'protein stabilization during protein complex assembly' I would instead create a general term 'protein stablization during protein folding' and leave it at that. The process of protein stablization is the same during protein folding and protein complex assembly. The proteins are sequestered to prevent aggregation. 2) Most of the protein folding processes use multiple chaperones. I am not sure what the intended use of this term "protein complex assembly, multichaperone pathway"was. I would just obsolete the term and create the new term chaperone-mediated protein complex assembly.

Rama

Original comment by: rbalakri

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2) I will propose obsoleting that multichaperone pathway term.

1) The trouble with adding a "general" protein stabilization during protein folding term is that at the moment, protein folding is a sibling of protein complex assembly - we'd need an additional term for stabilization during prot complex assembly.

It would be good to have a term to group protein folding and protein complex assembly (and all the processes involved in turning polypeptides into a 'finished' protein/protein complex) but I can't think of any word to encompass this.

Perhaps the easiest solution would be to use the existing term 'protein stabilization ; GO:0050821' and add something to the definition about preventing aggregation.

Original comment by: girlwithglasses

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Amelia,

1) Yes, please obsolete multichaperone pathway term.

2) I believe the term protein folding is already a grouping term (refers to all processes inolved in turning a single polypeptide or a complex into its final tertiary structure) and I don't think we need another one.

3) Part of the protein stablization process is to prevent it from aggregating. So, yes, that will clarify the matter.

Thanks a lot for all your efforts!

Rama

Original comment by: rbalakri

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OK, I have obsoleted 'protein complex assembly, multichaperone pathway' and added the new term 'chaperone-mediated protein complex assembly ; GO:0051131'. The protein stabilization def has also been altered.

If there are any outstanding problems / queries / grumbles with the chaperone term obsoletions, please let me know.

Original comment by: girlwithglasses

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• milestone: --> TermGenie
• assigned_to: nobody --> girlwithglasses
• status: open --> closed-fixed

Original comment by: girlwithglasses

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This term had mysteriously unobsoleted itself so I've sent it firmly back into the great obsolete bin in the sky.

Does anyone think it's worth having a 'chaperone-mediated transport' term for the chaperones that act as transporters? The existing transport chaperone functions are chaperoning metal ions around, so whether it would be worth differentiating between 'normal' ion transport and chaperone-mediated transport seems debatable to me. Any feelings on this?

Original comment by: girlwithglasses