Miami University

News Release

News and Public Information Office
Glos Center
Miami University
Oxford, Ohio 45056
(513) 529-7592
(513) 529-1950 fax
newsinfo@muohio.edu

Small changes lead to increased protective ability in disease-related protein; Study involved fish from the Antarctic to the tropics

04/05/2012

Share this Story:

photo: PLoS ONE, 7(3): e34438

Researchers from Miami and Ashland Universities and the National Institutes of Health have used a novel approach to show how evolutionary changes in a small heat shock protein have altered its ability to protect other proteins from damage during periods of physiological stress. The findings, published March 29 in PLoS One, provide a unique perspective on the function of these “stress proteins” and suggest ways that they could be altered to modify their protective abilities, according to Andor Kiss, Miami adjunct assistant professor of zoology and microbiology and one of the study authors.

The small heat shock protein (sHsp) alpha A-crystallin plays a role in the prevention of human diseases such as Alzheimer's, lens cataracts and cancer. By comparing the alpha A-crystallins from six different fish species living at temperatures from -2 to 40 degrees Celsius, the researchers were able to identify two small changes in the protein's structure that affected its stability and ability to buffer other proteins from stress.

After cloning the gene for alpha A-crystallin from the six different fish species, the study authors discovered that the protective function and stability of the resulting proteins correlated with the temperature of each fish. Using amino acid sequence and structural modeling analysis they identified specific amino acid differences between the warm adapted zebrafish and the cold adapted Antarctic toothfish.

By genetically engineering zebrafish alpha A-crystallins with amino acid substitutions found in the Antarctic toothfish the authors were able to show that two of these three changes alter alpha A-crystallin protective function in a predictable way.

“Not only does this add to our basic understanding of how small heat shock proteins work, but it validates a technique for identifying small heat shock protein modifications that could have therapeutic applications,” say Kiss and Mason Posner, professor of biology at Ashland University and lead study author.

Andor Kiss contributed to this article.

Classic approach

Lead study author Mason Posner, professor of biology at Ashland University, and Andor Kiss explain that:
“We have used a classic comparative biology approach to find how nature alters this small heat shock protein to function in different settings.
Most work on these proteins focuses on individual species, and usually mammals. By using fishes as a model group we have shown how comparing multiple species can identify small changes in protein structure with large effects on function, while still maintaining a viable molecule that does not cause disease.”

Antarctic toothfish. (Photo credit: Kevin Hoefling)