For one of OPIG’s short talks, I recently introduced the work done by Kotaro Tsuboyama et al. found in the paper A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation. As the name implies, HERO proteins have been found to retain function even after being boiled at 95C and have been found both in Drosophila and human HEK293T cell lines. Whilst it’s not impossible to find proteins which can “survive” 90+ Celsius, these are expected to be the reserve of extremophiles, not found in humans or fruit flies.
The team created supernatants of boiled and centrifuged lysate of Drosophila / Human cells and by performing liquid chromatography-mass spectrometry on the supernanant, discovered a large number of Hero proteins. “We identified 910 (S2 – Drosophila) and 980 (HEK293T) proteins with high confidence”.
Experimenting with these proteins, the team took Lactate dehydrogenase (LDH) from rabbit muscle, storing one sample in a buffer solution overnight, with a second sample in the lysate. Lo, the next day the buffered LDH had denatured but the HERO version was still functional. Further experimentation showing that Hero proteins seemingly “act as molecular shields to protect various ‘client’ proteins from denaturation even under stress conditions, such as heat shock, desiccation, and exposure to organic solvents.” However, these Heros do not appear to have the conserved motifs that would be found in other protective proteins, such as the late embryogenic abundant proteins found in plants, nor tardigrade disordered proteins found(stragely enough) in tardigrades.
Further work involved three different experiments relating to diseases associated with protein aggregation, including that of motor neuron disease. As the experiments used fly eye mutations as a model I’ll spare you that, but suffice it to say Hero proteins greatly reduced aggregation compared to the control. It should be noted that there was no “superhero” one-size-fits-all protein, instead different Heros prevented different types of aggregations.
Finally, flies Drosophila which were engineered to produce an overabundance of Hero proteins lived 30% longer than their control counterparts.
Whilst this was a whirlwind tour of the work, it does begin to “highlight potential biotechnological and therapeutic applications of Hero proteins”.
