University of Toronto scientists are helping to answer one of the most important questions in biochemistry, one that has implications for treating neurodegenerative diseases: how do proteins fold into their three-dimensional structures?
In research published in the July 29 issue of Nature, U of T post-doctoral fellow Dmitry Korzhnev and his supervisor, Professor Lewis Kay of the Department of Biochemistry, become the first researchers to characterize at an atomic level of detail the intermediate -- or substructure -- that forms as a protein folds to its 3-D state.
"Understanding how proteins fold is one of the Holy Grails of biochemistry," says Kay. "The intermediates that we can study make up only one or two per cent of the population of protein molecules in solution. It's hard to study them because they are present at such low levels. This is the first time we have been able to characterize an intermediate state at this level of detail."
Using nuclear magnetic resonance (NMR) spectroscopy, the researchers obtained data that allowed them to develop crude pictures of intermediate states for small, fairly simple proteins. They hope to refine their methods and apply them to other systems with intermediate states.
If scientists can understand the pathway a protein takes from one state to another, they may be able to predict protein structure, something that can't be done very reliably at present. The ability to accurately predict protein structure has implications for drug design, as well as for improving commercial products.
Understanding the pathway a protein follows will also help scientists understand errors in folding, a problem linked to diseases such as cystic fibrosis and Alzheimer's.
Professor Alan Davidson of the U of T Department of Medical Genetics and Microbiology, former U of T post-doctoral fellow Ariel DiNardo, Cambridge University post-doctoral fellows Xavier Salvatella and Michele Vendruscolo and Professor Christopher Dobson also contributed to this study. The research was funded through grants from the Canadian Institutes of Health Research, the European Commission, the Royal Society, the Leverhulme Trust and the Wellcome Trust.
Materials provided by University Of Toronto. Note: Content may be edited for style and length.
Cite This Page: