Monday, October 24, 2016
The phospho kiss of death!
I stole the idea for this post title from someone else, but its totally fitting for both the paper and for Halloween week!
You know how we normally figure out how a mechanism works in something really simple -- like a bacteria, and then we figure out how more complex organisms like us do things? This new paper in Nature from D.B. Trentini et al., shows us 2 super cool things:
1) Sometimes we figure out how the more complex organisms work first and
2) What the heck Arginine phosphorylation does!! (And this is why it is in Nature!)
We have to break down and get rid of old proteins. Or our cells will all just end up completely packed full of old proteins (sub-ideal). In us, that is one of the things that ubiquitination does. It marks old proteins for degradation so we can get them out of there.
Until now, there wasn't a clear understanding of how this works in prokaryotes. Turns out...it is mediated by arginine phosphorylation (at least in the awesome model gram positive Bacillus subtilis!)
They work out here that a protease called Clp (fitting?) selectively finds proteins with Arginine phosphorylation sites and eats them up. They find it by doing Clp pull-downs of normal and heat shocked cultures of the bacteria and then back it up by elegant in vitro assays as well as with knockout strains of bacteria. You couldn't be more thorough.
Interesting note here for us lab rats --
--can I actually post this? (Nature, please don't sue me, if this is a problem please see my contact info under disclaimers and I'll take it down!)
What is highlighted above -- I don't know how to do, but I think its awesome! Now that there are nanoflow UV detectors, does this mean I can rapidly determine during my runs my approximate tryptic digestion efficiency?? This bears further examination.
The phosphoproteomics is done with CID/ETD on an LTQ Orbitrap Velos Pro. (Unless there are 10 of them at IMP, this might be coming up on being the most famous Velos Pro in the world -- what a work horse!)
Anyway...super solid paper that absolutely deserves to be where it was published!!!