Okay - so - y'all ready for a cool sideways approach to find protein protein interacting pairs?
Is your first thought?
Ummm....don't we have 1 million of those? Like immunoprecipitation and affinity enrichments?
Sure - if you have an antibody to every protein in your organism. Do you have an antibody to every protein from a malaria parasite? We don't even have a good FASTA database for it.
Ummm...okay well we've totally got APEX and BioID!
Sure - you just need to convince someone to fund the development of hundreds of mutant strains of a parasite that pretty much only kills very very poor people. Again, we don't even have a very good FASTA database for this organism.
What about native CE complexosomics with a gaussian interaction profiler? WTF is that? It's a technique that can fill in the blanks I mentioned above!
Now - it doesn't look like a ton of fun - the other things are easier -but you basically lyse your cells under friendly enough conditions that you don't bust up the protein complexes and interactors. Then you take fractions by (in this case capillary electrophoresis) then you just digest everything in those fractions, analyze it like regular old shotgun proteomics. You need to use the Gaussian thing to backtrack your way to the interactors. It appears to be, in this case, totally compatible with MaxQuant label free output.
This is where I probably sorta get what is happening - but I think this is a lot like when we try to hunt down a natural product with an enzymatic reaction. If I have 30 fractions of all the small molecules that a weird mushroom/algae/or bacteria I've never heard of and fraction 6 has a little activity, 7 has a little more 8 has a ton, and 9 has an almost detectable amount - we start eliminating molecules by those that do/do not follow those trends. Ideally the one molecule with activity will perfectly track to that, right? As a disclaimer I send every request for natural product discovery to ANYONE else and if they strike out there then I'll do it. Has worked twice - in 2 decades.
Similar here - these gaussian models help backtrack the proteins that are most statistically within the clusters. Sounds smart, right?!? And if anything else can help you really backtrack to native protein-protein complex interactions in understudied organisms (and in this case a parasite- human interactions) I can't think of one. What a superb new tool for our utility belts!
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