USP14 reveals how much we've got left to learn about everything...

 

I've left this one open on my desktop for a really long time despite the fact I could use the space.

If you haven't seen it, maybe you don't want to, but I think it is worth rambling about for a second. 

Of course, my first thought was "wait. we know how a stupid proteosome works, right? RIGHT? Oh no...no...no...we don't...do we know how ANYTHING works? 

Turns out that we kind of do, but there was a big mystery here because increasing the amount of USP14 that is around will both upregulate and downregulate the amount of proteosomal activity. LCMS based proteomics didn't solve this one, though. CryoEM with machine learning figured this one out.

And, if I have this right (here is the original paper, btw) the amount of USP14 around is completely irrelevant to this system. The amount of modified (by ubiquitin/ubiquityl) USP14 around is all that matters. Makes you kind of wish these mods weren't such a strangely hard thing to work with, right?