Phosphoproteome -- readers, writers, and erasers

This is diagram I made that was featured in a poster session at the annual conference of Experimental Biology, 2019. This is an alignment of 2 paralogs of TopoIsomerase between species. The small colored boxes with letters in them represent amino acids, and the arrows pointing to the boxes from the top and bottom indicate various post translational modifications (PTMs) with the purple arrows indicating PTMs of the phosphorylations variety. The collection of all such phosphorylations in the proteome might be called the “phosphoproteome.”

When estimating the improbability of forming proteins by chance and/or selection, consideration of the PTMs should be taken into account. Multicellular mammals leverage PTMs much more than their unicellular eukaryotic counter parts like yeast.

One can see the density of PTMs on certain segments of the Topo 2 enzyme in my diagram created by MEGA and some MS Paint:

The notion of a Phosphoproteome is now an accepted buzzword as evidence by this wiki entry:

Phosphoproteomics - Wikipedia

phosphoproteomics provides two additional layers of information. First, it provides clues on what protein or pathway might be activated because a change in phosphorylation status almost always reflects a change in protein activity. Second, it indicates what proteins might be potential drug targets as exemplified by the kinase inhibitor Gleevec. While phosphoproteomics will greatly expand knowledge about the numbers and types of phosphoproteins, its greatest promise is the rapid analysis of entire phosphorylation based signalling networks.

Here is something I encountered just today on the importance of phosphoproteomic activity:

The collapse and reassembly of the nuclear lamina is controlled by the phosphorylation and dephosphorylation of the lamins. Phosphorylation of lamins by protein kinases (discussed in Chapter 4) weakens the interactions between the lamin tetramers and causes the filaments to fall apart. Dephosphorylation by protein phosphatases at the end of mitosis allows the lamins to reassemble (see Figure 18–30).

Alberts, Bruce. Essential Cell Biology (Fifth Edition) (p. 578). W. W. Norton & Company. Kindle Edition.

I’m not planning to comment immediately on its relevance to ID and evolution, except to say the sentiment in the ID community is that the phosphoproteome is a challenge to evolutionary theory because of the difficulty it create for evolving signalling networks. Instead, I’d like to use this thread to collect stunning examples of the phosphoproteome’s significance in biology.

Even in that example by Alberts, the importance of a working choreography of the phosphorylation “write” and “erase” of the phosphorylation marks on lamins appears life critical. It is nice to see this now appearing in undergrad textbook cell biology!

Even in peer-reviewed literature the notion that there are “readers”, “writers”, “erasers” somewhat like in the computer field is now used to describe the processing within the phosphoproteome and other PTMs.