Strange, Extremely Disordered Proteins Are Heroes in Disguise – Protect Other Proteins

 


Around 2011, when graduate student Shintaro encountered an unusually heat-resistant protein that increased the stability of Argonaut, the protein at the center of the lab's research, the Hero protein was discovered by accident. At R-I K E-N, Shintaro now runs his own lab.


Although it was interesting to learn that Argonaut's behavior was improved by a strange, extremely disordered, heat-resistant protein, its biological significance was unknown, and the protein's sequence appeared to have no connection to anything else So, since we didn't know what to do next, we just decided to put it off for years, stated Professor T O M-A R-I, who led the research lab and was the paper's final author.


K O T-A R O Tsuboyama eventually saw the hero-hero k U N protein in a new light, first as a doctoral student and then as a postdoctoral researcher


An unlikely discovery

Around 2011, when graduate student Shintaro encountered an unusually heat-resistant protein that increased the stability of Argonaut, the protein at the center of the lab's research, the Hero protein was discovered by accident. At R-I K E-N, Shintaro now runs his own lab.


Although it was interesting to learn that Argonaut's behavior was improved by a strange, extremely disordered, heat-resistant protein, its biological significance was unknown, and the protein's sequence appeared to have no connection to anything else So, since we didn't know what to do next, we just decided to put it off for years, stated Professor T O M-A R-I, who led the research lab and was the paper's final author.


K O T-A R O Tsuboyama eventually saw the hero-hero k U N protein in a new light, first as a doctoral student and then as a postdoctoral researcher


Heroes in disguise

Even between species, proteins with similar functions typically have similar amino acid sequences. This is known as "evolutionary conservation" by experts. 


It is challenging to predict Hero protein's function or even identity due to the lack of evolutionary conservation that T O M-I R-I group discovered when they first identified Hero K U N. This lack of conservation appears to be a defining feature of hero proteins.


To uncover the genuine personalities of more Legend proteins, analysts developed human and organic product fly cells in the lab, made separates from the cells, then basically bubbled them.


Chemical interactions that support a protein's structure are typically weakened by high temperatures, causing it to unfold and clump with other unfolded proteins.


Heat typically damages proteins, but we discovered that Hero proteins remain functional even at 95 degrees Celsius (203 degrees Fahrenheit). It is a piece unusual, which is the reason I think nobody has painstakingly portrayed these proteins previously, said Tsuboyama.


The next step was to use mass spectrometry, an analytical method, to find any proteins that were still present in the boiled test tubes.


They discovered hundreds of hero proteins in humans and fruit flies


Heroes to the rescue

Six hero proteins were chosen by him for in-depth research. 

Despite high temperatures, drying, or harsh chemicals that would normally destroy them, some of the six hero proteins mixed with other "client" proteins maintained their shape and function. 


High levels of Hero proteins prevented cells from forming the protein clumps that are characteristic of the neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS) and restored their normal growth patterns in lab-grown human motor nerve cells. 


Fruit flies' large, sensitive eyes are often used as disease models because mutations that cause neurodegeneration in humans deform them. The researchers discovered that increasing hero activity prevented ALS-associated protein clumps from deforming the eyes of flies. On the other hand, removing normal Hero activity harmed the fly eye's development.


In addition, when researchers genetically modified healthy fruit flies to have high levels of individual hero proteins throughout their entire bodies, they discovered evidence that hero proteins can promote longevity. Amazingly, some hero proteins extended the lifespans of flies by 30%. 

T O M-A R-I commented, "It appears that hero proteins naturally exist to keep other proteins happy"

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