BATON ROUGE -- An LSU chemist and his colleague from the University of Minnesota have made some important discoveries about a common human protein that could eventually lead to treatments for both Type 2 diabetes and obesity.
LSU biochemist Vince LiCata and his colleague David Bernlohr of the University of Minnesota have published their findings in the December issue of the scientific journal, Proteins: Structure, Function and Genetics. An image depicting their findings is featured on the journal's cover.
The image comes from calculations the two have performed on a family of proteins known as lipid-binding proteins. Lipid-binding proteins are relatively small molecules found in nearly every human tissue, often in great quantities. The figure shows the distribution of electronic charge on the surface of the proteins -- a significant discovery by LiCata and Bernlohr about how the molecules work.
The proteins bind fatty acids and other lipids processed by tissues and cells and have been directly implicated in the development of Type 2 diabetes. Because they interact with all the fats that enter the body, they are also a focus in the development of obesity.
"There are a number of mysteries surrounding these proteins," LiCata said. "First, they bind their fatty partners in a deep interior cavity, so it is unclear how other cellular components can tell what lipid is inside the protein, or even if there is a lipid inside the protein."
Cellular machinery uses the proteins to sort the different types of fat for distribution to different parts of the cell, and to carry the fat, which is insoluble in water, to its destination. Some genes, for instance, are turned on or off by fatty acids, and the lipid-binding proteins help get the fats into the nucleus where they can do their work.
"Another mystery involves the fact that nearly every tissue in the body has its own distinct lipid-binding protein, yet all of these different family members have very much the same three-dimensional structures."
Usually, it is the shape of a molecule that determines its function, but because the structures are almost identical, LiCata and Bernlohr asked what other information the proteins might hold besides their shapes.
What they found was that the proteins from different parts of the body have very different electronic surface patterns. Regions where a protein from fat tissue is positively charged will be negatively charged in a protein from liver tissue, even though the underlying three-dimensional shapes of these regions are nearly identical.
These different electronic charge patterns mean these proteins will perform very different tasks in different tissues, a fact previously not recognized because their nearly identical shapes fostered the belief that they would be performing the same tasks in every tissue.
In addition, LiCata and Bernlohr discovered that the proteins expand slightly when they sequester their lipid partners. Because the expansion is usually less than 3 percent, it was not previously detected, but to a cell, a 3 percent change in size would make an enormous difference, LiCata said.
The researchers' findings suggest solutions to a number of more subtle questions that surround these proteins, and LiCata said he plans to extend his calculations to finer levels of detail and perform direct experimental manipulations on the different lipid-binding proteins based on the findings from his calculations.
The above post is reprinted from materials provided by Louisiana State University. Note: Materials may be edited for content and length.
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