Chaperones

Intro

As part of the transporter activity overhaul it has become apparent that the chaperone terms need some work. We are planning to do this straight after the transporter activity implementation goes live.

Background

The most recent email thread (March 2007):

Val 26 Mar 2007 18:08:20

Summary, as I understand it: (CCing Midori too...Midori do you remember any lurking SF entries or action items relating to this?)

'metallochaperone' and 'protein folding chaperone' will be direct children of 'molecular function'

ONLY 'protein transport chaperone' will be a child of transporter activity

NONE would have any term or relationship under 'transmembrane transporter activity'

(Need to explain a bit about why this is necessary)

The only SF entry I can see is mine here [1233407] but I'm sure this has been discussed in other SF items and possibly even at annotation camp. Jen can you find any other background for this? it would give it more weight.....

If you two could comment, then Jen perhaps this could go to the transport interest group, Maria, Rama, and David for further comments?

This is my first attempt

I propose we resurrect this and the def (or something very similar)

chaperone activity

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.
This term was made obsolete because, as defined, it represents a class of gene products rather than a molecular function. The term string is also ambiguous, having connotations of involvement in transport processes. To update annotations, consider the molecular function term 'unfolded protein binding ; GO:0051082' and the biological process term 'protein folding ; GO:0006457' and its children.

rename as
protein folding chaperone activity
synonym chaperone activity
Assists in the correct non-covalent assembly of polypeptide-containing structures in vivo, by binding unfolded proteins to stabilize and prevent aggregation. Chaperones do not form a part of the assembled structures when they are performing their normal biological function.

protein transport chaperone

A protein which recognises and binds a protein substrate and transports it within the cell via a protein trafficking mechanism.???

a child would be protein carrier activity and would have a def consistent with the eventual def for protein transport chaperone

a child of this would be
GO:0008262 : importin-alpha export receptor activity (gene product)
renamed to:
nucleocytoplasmic protein carrier activity
This would deal with SF [1455372]

metallochaperone activity

Assists in the delivery of metal ions to target proteins (need to extend this def)

Midori 26 Mar 2007 20:51:36

I can't think of anything else open on SF. There are some closed items that may provide background; search for 'chaperone'.

1. I would definitely leave the old chaperone term (GO:0003754) obsolete, because it was used sloppily when it was 'live', as though it meant both protein folding chaperone and transport chaperone. A new 'protein folding chaperone activity' term should get a new ID; I might also massage the definition a little, e.g. 'interacting selectively with unfolded proteins, thereby assisting in the correct non-covalent assembly of polypeptide-containing structures in vivo, and preventing aggregation. Chaperones do not form part ...' Finally, could it go under protein binding?
2. The definition of protein transport chaperone starts off with 'a protein which' ... that won't do as a definition of an activity (and if it's not an activity, it doesn't belong in the function ontology). Maybe 'interacting selectively with a protein substrate and transporting it within the cell'? Also not sure what a 'protein trafficking mechanism' is, so that bit might need a bit more explanation.

Val 27 Mar 2007 11:28:58

I would definitely leave the old chaperone term (GO:0003754) obsolete, because it was used sloppily when it was 'live', as though it meant both protein folding chaperone and transport chaperone. A new 'protein folding chaperone activity' term should get a new ID; I might also massage the definition a little, e.g. 'interacting selectively with unfolded proteins, thereby assisting in the correct non-covalent assembly of polypeptide-containing structures in vivo, and preventing aggregation. Chaperones do not form part ...' Finally, could it go under protein binding?

Yes to all

The definition of protein transport chaperone starts off with 'a protein which' ... that won't do as a definition of an activity (and if it's not an activity, it doesn't belong in the function ontology). Maybe 'interacting selectively with a protein substrate and transporting it within the cell'? Also not sure what a 'protein trafficking mechanism' is, so that bit might need a bit more explanation.

OK I know my defs were crap and you'd be able to sort them;)

I went digging about in my archive and the Protein trafficking suggestion is wrong for nucleocytoplasmic transport if we follow this wisdom from john Armstrong:

"'Protein targeting' means targeting individual proteins to specific organelles e.g. the ER, the mitochondria, the peroxisome, the nucleus. 'Protein traffic' means moving groups of proteins and lipids in vesicles between organelles."

So if nucleocytoplasmic transport comes under targeting--targeting is dependent on some intrinsic sequence in the protein. There is always some dependency on a signal sequence for nucleocytoplasmic transport (either within the protein or within a protein that the transported protein is attached to)

This agrees with this description from Shelly Sazer:

"There are two types of "classical" NLS whose sequences have been defined and have pretty reliable consensus sequences. These are the SV40 mono-partite NLS and the nucleoplasmin bi-partite types of NLS, and generally when people talk about NLSs they are referring to this type. These proteins are imported to the nucleus by a complex of importin alpha and importin beta. There are other proteins that do not have a classical NLS and bind directly to importin beta for import, but the consensus sequences for this has not been defined. Lastly, there are proteins that do not have any NLS but bind to another protein that contains an NLS which is responsible for transporting the protein into the nucleus. So, amongst this second class are proteins that do not have a "classical" NLS, but if we take the definition of NLS as a sequence that directs a protein to the nucleus, then these proteins do have an NLS."

so......How about

protein transport chaperone

'interacting selectively with a protein substrate and transporting it within the cell'

This mechanism is dependent on a protein targeting mechanism which requires a signal sequence within the transported protein or one of its binding partners ?

Although this would not work for some things which are currently annotated to protein carrier. Some COPII vesicle proteins which are annotated to this term (although I'm not sure that they should be?).....these work by a trafficking mechanism

Also, can we make it clear in the def somehow that this does not refer to targetting across a membrane (i.e ER translocation etc)

In fact, Jen, this is another term we need to consider at this point:

SNAP receptor activity is a child of intracellular transporter activity and has the very 'untransporty' def:

Acting as a marker to identify a membrane and interacting selectively with one or more SNAREs on another membrane to mediate membrane fusion.

perhaps

protein binding
--protein transport chaperone
----nucleocytoplasmic protein transport chaperone
--SNAP receptor activity
--protein folding chaperone

transporter activity
----protein transport chaperone
----nucleocytoplasmic protein transport chaperone

obsolete protein carrier (used in different contexts)

ther term name "protein transport chaperone" bothers me a bit. What we mean here is a 'chaperone type transporter' Is there a better 'term name?'

Any closer?