Wednesday, December 11, 2024

Proteoform level analysis of "purified" albumin reveals shocking levels of complexity!

I'm again going to put off blog posts on the 50,000 human proteome cohorts using "next gen" spot-based targeted proteomics.

I get it - I love the idea that we can use alternative technologies and get to this kind of population level protein level studies. But -just to remind you - we don't know the answer to this question


What we do know - without any possible doubt, whatsoever, that evolution is super ridiculously stingy when it comes to making new stuff. Sure, there are excessive things that don't negatively impact the overall survival of a population - but those are exceedingly rare.

If a cell makes an alternative form of a protein you can almost guarantee that there is a good fucking reason for it. 

Case in point - what if you treated one of the single best characterized proteins on the planet - not as a protein - but as a proteome

This team took a look at multiple "purified" forms of trusty old bovine serum albumin and treated it like a population of proteoforms - and 

1) It definitely is

2) "Purifying" a protein is....umm... something you'd think was 100% super well defined. Let's go with "could use further definition and characterization". 

We've seen things like these in the past - here is an old post where a modified Exactive (I think what later became the Exactive EMR, one of my all time favorite little boxes) - pulled out 59 different forms of ovalbumin. 

That's hard to look at and really encapsulate. Woodland et al., went full classic protein biochemistry and - this isn't hard to understand. This is a "purified albumin" separated out by isoelectric focusing in dimension 1 and by SDS-PAGE in dimension 2. 


This is a purified protein??? Some of that stuff probably was just tagging along, but a whole ton of that is albumin proteoforms. And - again - there is probably a very good reason for why an organism would expend energy to develop alternative forms of all these proteins, right? 

This is a super cool and thought provoking study that pokes some holes in more than a couple of our normal assumptions. 

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