Editor's Choice Main Category: Biology / Biochemistry Article Date: 20 Jun 2012 - 11:00 PDT

Current ratings for: 'How Protein Clumps Are Pulled Apart'

In humans, amyloid fibers form biological nanostructures that house pigments and other molecules, and may also play an important role in long-term memory. These fibers are one of the most stable protein-based structures in nature, so when they are harmful in diseases, such as Parkinson's, they are extremely difficult for cells to break down.

As a result, Martin Duennwald and AnaLisa Echeverria, at the Boston Biomedical Research Institute, and James Shorter, assistant professor of Biochemistry and Biophysics at the University of Pennsylvania, set out to find ways to promote beneficial amyloid fiber assembly or to reverse its pathogenic assembly, at will. The study is published in PLoS Biology.

Yeast have a protein called Hsp104 that can quickly disassemble amyloid fibers, and this activity is significantly enhances by a group of small heat shock proteins. However, humans and other animals do not have the Hsp104 protein, thus raising the question of whether human cells are also capable of disassembling amyloid fibers?

In this study, the researchers found that when Hsp104 is absent, the yeast small heat shock proteins work together with other proteins to disassemble amyloid fibers. The proteins slowly remove each subunit one by one from the tips of the fibers. The team were surprised by this activity as these proteins are best known for their role in preventing protein clumping.

Shorter explained:

According to the researchers, the proteins of the amyloid-disaggregating machinery in yeast are also present in humans. Therefore, human small heat shock proteins are able to work together with other proteins to disassemble amyloid fibers, even without Hsp104.

They state that these findings could lead to the development of new therapies for different neurodegenerative disorders.

Their aim is to activate the machinery in humans to pull apart disease-causing amyloid fibers where and when needed by increasing the expression of heat shock proteins.

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How Protein Clumps Are Pulled Apart