Obsolete GO:0051673 membrane disruption in another organism

[pgaudet]

Dear all,

The proposal has been made to obsolete GO:0051673 membrane disruption in another organism. The reason for obsoletion is that this term represents a molecular function, 'pore forming activity' (requested in #24007)

This term has no annotations, no mappings, and is not present in any subsets. You can comment on the ticket: https://github.com/geneontology/go-ontology/issues/24008

Thanks, Pascale

[pgaudet]

In fact there were annotations, apologies

Group	Number of EXP annotations
AgBase	3
CACAO	5
MGI	2
UniProt	26
WB	2

[genegodbold]

Hey @pgaudet, I would argue that there are at least two ways to disrupt a membrane. Phospholipases (PLA, PLC, PLD) can destabilize phospholipid bilayers by basically chewing on/through them. I've documented at least a couple dozen bacterial proteins that have this activity which is NOT pore forming. Then there are a variety of pore-forming proteins like aerolysin, leukotoxin LtxA, Anthrolysin, Cerolysin, Listeriolysin O and scores of others that bind to something (often cholesterol) in the metazoan membrane and then oligomerize to make a pore. These are classic pore-forming proteins.

[genegodbold]

There are venom components that are phospholipases (PLA) that also disrupt target cellular membranes: Basic phospholipase A2 RV-4 from Daboia siamensis (UniProt Q02471); acidic phospholipase A2 (UniProt Q6EAN6) which probably inhibits neuromuscular transmission by blocking acetylcholine release from the nerve terminal (not chewing on membrane).

Cupiennin-1d (UniProt P83622), a linear peptide of 35 residues and a component of spider venom, is hemolytic for human erythrocytes with a median lethal dose of ~14.5 micromolar and is also insecticidal with a medial lethal dose of under 10 micomolar [PMID11792701].

Css54 (UniProt P0DL41) is a scorpion venom component that probably does much the same, Css54 was hemolytic against human erythrocytes: at a concentration of 25 micromolar, 83% of red blood cells were lysed [PMID23093034].

Verrutoxins from hornets also disrupt membranes. Verutoxin-2b is a potent allergen and is hemolytic for mouse erythrocytes (99% hemolysis at 3 micrograms/ml) [PMID10484737].

There are others as well.

[pgaudet]

Great, that's a great start for next week's discussion.

[addiehl]

Also I would point out that the 'activation of membrane attack complex' is a process that is a type of membrane disruption in another organism though not indicated as such by the GO hierarchy. The MAC forms a pore consisting of a complex of complement proteins.

Similarly the formation of the perforin pore by oligomerization is a multistep process leading to formation of a pore that disrupts a membrane, although representation of this process in GO is missing.

[genegodbold]

The MAC usually isn't forming IN another organism, but rather in the host organism ON the surface of a bacterial cell, virally-infected host cell (poxviruses encode proteins like SPICE that inhibit complement), or fungal cell (pathogenic yeast encode complement-inhibiting sequences).

[deustp01]

apologies for the tangent, relevant to pathways2GO project: @ukemi should we take a look at pathway R-HSA-166665 "terminal pathway of complement" and the GO-CAM model derived from it (and a mouse model to be built from it?) keeping this discussion in mind and looking for ways to bring this process fully into GO?

[ukemi]

Yep. I will put it in out project so we don't forget. https://github.com/geneontology/pathways2GO/issues/207

[addiehl]

Well the MAC is inserted into the membrane of the other organism, so it does seem to be "in another organism" even if that organism is located in a host organism.