Cell protein interactions favor fats

Mar 22, 2012

For cells to signal each other to carry out their vital work, could the cell membrane's lipids -- or fats -- play a role in buttering-up the process? A research group led by University of Illinois at Chicago chemistry professor Wonhwa Cho thinks so, and presents detailed findings in the April 27 issue of Molecular Cell, online March 22.

Proteins -- molecular machines that process signals critical for cell function and regulation -- perform their work by forming complex and tightly regulated interaction networks. Until recently, most scientists thought interactions were very tight and specific. But research now indicates that is not the case.

Cho has studied cell membranes for more than two decades and has long hypothesized that membrane lipids play a critical role in regulating cellular protein interactions. To convince skeptics, he and his team conducted a genomic-scale investigation into if, and how, lipids play this role.

"Cellular protein interactions are mediated by so-called domains, or PIDs. These are small molecular structural units within large proteins that specialize in recognizing interaction partners," he said.

"We decided to characterize PIDs in the whole genome and determine how many are regulated, by which membrane lipids, and how it's done."

For their they selected the PDZ domain, one of the most abundant in and a target for drug development. Developing therapies based on protein interactions is a major field of biomedical research, but a better understanding of protein is needed.

Due to the large number of PDZ domains, it was impractical to characterize all of them experimentally. So Cho, working with UIC computational scientist and associate professor of bioengineering Hui Lu, his graduate student Morten Kallberg, Columbia University colleague Barry Honig and Honig's postdoctoral assistant Antonina Silkov, performed bioinformatics computations to predict and classify the functions of all lipid-regulating PDZ domains using an experimental database collected by Cho's postdoctoral assistant Yong Chen and graduate student Ren Sheng.

Cho said the group found that "an unexpectedly large number" of PDZ domains -- more than 30 percent -- interact with various membrane lipids, and that lipids control their cellular location and interaction with other protein partners.

"Furthermore, different PDZ domains are regulated by different lipids in different mechanisms, which open new avenues for drug development for specific control of cellular activity of PDZ domains implicated in major human diseases," he said.

The findings will be available online in a searchable format for other researchers working on PDZ domains.

Cho and his group have since used their PDZ approach to study the other major protein interaction domains. He said they've collected substantial data and will soon report findings showing that lipids control cellular location and function in the other domains as well.

Cho said his next major step is to develop a new and novel class of small molecules that specifically modulate binding activity of protein interaction domains to control diverse, dysfunctional cellular signaling pathways which cause cancer, diabetes and other inflammatory and metabolic diseases.

Explore further: DNA may have had humble beginnings as nutrient carrier

Related Stories

Chemists get grip on slippery lipids

Aug 30, 2007

The ability of the body's cells to correctly receive and convey signals is crucial to good health. Lipids, or fats, play a critical role in this regulation by providing spaces for proteins to gather and network. They are ...

Recommended for you

Research helps identify memory molecules

7 hours ago

A newly discovered method of identifying the creation of proteins in the body could lead to new insights into how learning and memories are impaired in Alzheimer's disease.

Computer simulations visualize ion flux

9 hours ago

Ion channels are involved in many physiological and pathophysiological processes throughout the human body. A young team of researchers led by pharmacologist Anna Stary-Weinzinger from the Department of Pharmacology ...

Neutron diffraction sheds light on photosynthesis

9 hours ago

Scientists from ILL and CEA-Grenoble have improved our understanding of the way plants evolved to take advantage of sunlight. Using cold neutron diffraction, they analysed the structure of thylakoid lipids found in plant ...

DNA may have had humble beginnings as nutrient carrier

Sep 01, 2014

New research intriguingly suggests that DNA, the genetic information carrier for humans and other complex life, might have had a rather humbler origin. In some microbes, a study shows, DNA pulls double duty ...

Central biobank for drug research

Sep 01, 2014

For the development of new drugs it is crucial to work with stem cells, as these allow scientists to study the effects of new active pharmaceutical ingredients. But it has always been difficult to derive ...

User comments : 0