Protein regulation mechanisms conserved for millions of years

Protein regulation mechanisms conserved for millions of years

29 Apr 2019 - 10:00

About the study

  • Researchers discovered protein regulatory switches (phosphorylation sites) conserved across diverse eukaryotic species (organisms whose cells have a nucleus enclosed within membranes)
  • Humans share identical protein regulatory switches with single-celled organisms, showing these mechanisms have existed for hundreds of millions of years
  • Only 5% of all such regulatory switches are widely conserved, but this degree of conservation indicates these mechanisms may be fundamental to life

April 29, Cambridge – Researchers at EMBL’s European Bioinformatics Institute (EMBL-EBI), the University of Zurich and collaborators have identified protein phosphorylation sites (protein regulatory switches) which are ultra-conserved across the eukaryotic tree of life.

What is protein phosphorylation?

Proteins are the workforce of a cell and act as factories that perform almost all the essential tasks within the cell. Proteins are made by following instructions encoded in DNA in a process called translation. Once they are made, the way proteins function can still be altered by the addition of reversible modifications. These can be imagined as switches within a protein, known as post-translational modifications. One of the most frequent modifications that can occur is phosphorylation. Phosphorylation can change the way a protein works in a myriad of ways, including marking it for destruction or more subtly by altering the way it interacts with other proteins.

The findings, published in Nature Communications, show that these ultra-conserved sites have been present for hundreds of millions of years and therefore may be fundamental to life.

By combining 537,321 phosphosites from 40 eukaryotic species to identify phosphorylation hotspot regions in proteins, the researchers were able to identify that 5% of all switch sites in proteins were highly conserved across species.

Impacting protein regulation

“Ultra-conserved phosphorylation events are rare, but of course they are expected to be significant,” says Pedro Beltrao, a Group Leader at EMBL-EBI and lead author of the paper. “After we defined these events, we also looked at where they are positioned in the proteins. As you might expect, they tend to be in regions of the proteins which are very important in regulating their activities, or the way they interact with each other.

A protein regulatory switch can impact the way in which a protein behaves, for example activating or deactivating it. The study reveals that single-celled organisms share some of the same protein switches as complex multicellular species, such as humans.

“These positions have been regulated for hundreds of millions of years, and haven’t changed,” adds Beltrao. “These are regions which are fundamentally important for the regulation of proteins, across all eukaryoticlife. If you were to travel back in time several hundreds of millions of years, these switches would still be there. Anything that is so conserved has to be fundamental for life, otherwise it would not have made it this far.”

What next?

Having identified the ultra-conserved protein phosphorylation sites, the researchers’ next step will be to introduce mutations to these regions in order to understand the specific roles they play within protein regulation.

Source articles

Strumillo MJ., et al. (2019). Conserved phosphorylation hotspots in eukaryotic protein domain families. Nature Communications. Published online 29 04; DOI: 10.1038/s41467-019-09952-x

Contact the news team

Oana Stroe
Communications Officer
stroe@ebi.ac.uk
+44 (0)1223 494 369

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