Saturday, November 16, 2013

59 proteoforms of ovalbumin?

I'm currently just overwhelmed in my raw appreciation of just how cool science is and of how very very little we seem to know about our world around us.  There is stuff to discover absolutely everywhere!

Case in point, this new paper out of Albert Heck's lab where they use a modified Exactive (essentially the Exactive plus EMR) to study ovalbumin in its native state.  The same ovalbumin that we use as a molecular weight marker for SDS-PAGE.  The same ovalbumin that is sitting on a fridge shelf for some reason or another in virtually every lab in the world.

And what do they see in their nifty native analysis?  59 proteoforms!  59 distinct variations of this standard protein.  Seriously?  59?!?!  Does that blow anyone else's mind a little?

Step sideways a second:  Remember the human genome project release?  When we were super excited that we had 30,000 genes sequenced or whatever after close to a decade of work? (I drank a lot of beers yesterday with a friend who told me that he can sequence a human genome with 30x coverage in 1 day, but that's a different thought for a different day).  So we had 30k genes all worked out, and that is a lot of complexity.  But even if we ignore all the variations in transcription/translation that we know about now, and just considered  that if 1 gene made one transcipt and that transcript made one protein, here we see 59 variants of that protein that, for the most part we couldn't/wouldn't find (or it would be pretty difficult to discern) unless we looked at the protein in its intact and native state.  That is a lot of complexity!  But think about the fact that we know there are possibly millions of protein variants at just the linear amino acid/modification level, and throw in the fact that these can actually result in a much larger combination of proteoforms and Wow!  does that ever make it seem amazing that we have come so far, but also how exciting how much further we have to go?!?!

Overwhelming feeling here?  We all need to do more intact and native analysis.  (In a related note, this week I'll be doing some top-down work on a QE Plus with the Protein Mode upgrade {Woooohoooo!}.  Of course, my opinions/results on that will follow!)

Check out this paper.  If only to get an idea about how many things biologically kind of make sense, but don't really, that might make sense if we took into account the fact that what we think of as 1 protein could actually be dozens of variants that we just haven't had the tools (until now!) to even see.

The paper that has inspired me to get out of bed with a ton of appreciation for the world today is called:

Analyzing Protein Micro-Heterogeneity in Chicken Ovalbumin by High-Resolution Native Mass Spectrometry Exposes Qualitatively and Semi-Quantitatively 59 Proteoforms

TL/DR:  Read this paper.

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