Hero Proteins Protect Against Protein Clumps

Researchers at the University of Tokyo have discovered a new group of proteins that they say can protect against protein clumps associated with neurodegenerative diseases.  These so called Hero proteins can reportedly protect other proteins, extend the life span of fruit flies by 30 percent, and protect both fruit flies and lab-grown human motor neurons from dangerous protein clumps.

The Hero protein was identified by accident in about 2011 when then-graduate student Shintaro Iwasaki encountered an unusually heat-resistant protein that increased stability of Argonaute, the protein at the center of the lab's studies.  "It was kind of cool to know that a strange, extremely disordered, heat-resistant protein improved the behavior of Argonaute, but its biological relevance was unclear and, moreover, the protein's sequence seemed unrelated to anything else. So, we didn't know what to do next and just decided to put it on the shelf until years later," said Professor Yukihide Tomari, senior author of the paper published today in PLOS Biology.

The lack of evolutionary conservation that Tomari's team encountered when they first identified hero-hero kun seems to be a defining characteristic for Hero proteins, making it difficult to predict their function or even identity. To uncover the true identities of more Hero proteins, researchers grew human and fruit fly cells in the lab, made extracts from the cells, then simply boiled them.

High temperatures normally weaken chemical interactions that support a protein's structure, causing it to unfold and clump together with other unfolded proteins. "Proteins are generally damaged by heat, but we found that Hero proteins remain intact even at 95 degrees Celsius without losing function," said Tsuboyama. Next, researchers mass spectrometry to identify any proteins that remained in the boiled test tubes. They found hundreds of Hero proteins in fruit flies and in humans.

Tsuboyama selected six Hero proteins to study in detail. When some of the six Hero proteins were mixed with other "client" proteins, those clients kept their shape and function despite high heat, drying, or harsh chemicals that would normally destroy them.

In experiments using lab-grown human motor nerve cells, high levels of Hero proteins stopped cells from developing the protein clumps characteristic of amyotrophic lateral sclerosis and restored their normal growth patterns.