folding proteins

Healthy brain protein links to Parkinson’s

USC (US) — Structural clues about a protein commonly found in healthy brains may lead to finding a cure for Parkinson’s disease.

The alpha-synuclein protein is a major component in the protein clumps found in Parkinson’s. Unlike most proteins, which are typically rigid and occur in one definitive form, the alpha-synuclein protein is able to fold and change its structure.

New research, published in the Journal of Biological Chemistry, finds that the energy difference between two particular alpha-synuclein structures is less than previously thought.

“We’re trying to understand the mechanisms of protein folding and misfolding,” says Tobias Ulmer, assistant professor of biochemistry and molecular biology at the University of Southern California.

“Then we can say why something is going wrong, which is essential to treating neurodegenerative disorders like Parkinson’s.”

Usually, if proteins misfold, they are repaired or they break down. But  when the alpha-synuclein protein misfolds it aggregates and becomes toxic to surrounding nerve cells. Understanding its folding and finding what causes aberrant folding is key to determining the root cause of the disorder, Ulmer says.

Ulmer compares the energy that researchers thought was needed to change the protein’s structure to hurricane-force winds and the actual energy required to a light summer breeze. Experiments measured the energy of elongated and broken helix forms of alpha-synuclein through circular dichroism spectroscopy, fluorescence spectroscopy, and isothermal titration calorimetry.

“There may be a continuous interconversion between folded alpha-synuclein structural states that might contribute to its pathological misfolding,” says post-doctoral research associate Sowmya Bekshe Lokappa, the study’s co-author.

“But we need to have even better insight into the mechanisms of protein folding and misfolding to explain what’s going wrong in the brain.”

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