September 19, 1997

Investigators discover new regulator of protein interaction

Investigators discover new regulator of protein interaction

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Marcia Newcomer, Ph.D., is studying a new type of structure that allows proteins to communicate. (Photo by Donna Marie Jones)

Vanderbilt University Medical Center investigators have identified a new type of structure that allows proteins to communicate, one that could shed new light on how cell life is regulated.

Many proteins contain domains that help regulate interactions with other proteins. In some of these proteins, this communications center is called the SH3 domain. It's here that VUMC investigators documented what could be a new type of communication regulator.

³In the study of the Eps8 protein we discovered an unusual formation of the SH3 domain that may provide for a very different type of interaction between molecules,² said Marcia E. Newcomer, Ph.D., associate professor of Biochemistry.

Results of the study of protein interactions were recently published in Nature Structural Biology.

The EPS8 protein was investigated because it is one of many communication centers in the cell. An understanding of how it communicates with other proteins may lead to a clearer picture of how it affects cells growth, said Newcomer.

This previously undiscovered molecule formation could lead to new treatments for a number of different diseases once its action is understood, Newcomer said.

Using x-ray crystallography, researchers studied protein molecule formations by looking at an indirect image cast by x-rays aimed at the molecule.

³This is not like taking an x-ray of the chest where you can immediately see the outline of the bones and the lungs,² said Newcomer.

Working backward from the different angles of x-rays that reflect off the protein, Newcomer can decipher the protein's shape.

All of the proteins in the human body depend on their structure to dictate their function and their ability to recognize the other proteins they interact with.

³If you want to know what a molecule does or why it doesn¹t work correctly, then it is very important that you know what it looks like and how it might fit together with other molecules,² said Newcomer.

Newcomer hopes that once the form of different molecules is understood, other scientists will be able to devise a way to repair malfunctioning proteins.

Almost all proteins with SH3 domains are involved in some type of control of cell growth. Uncontrolled cell growth, which is a simplistic description of cancer, may be spurred when the lines of communication between molecules within the cell break down, said Newcomer.

The SH3 connection on the Eps8 protein is unlike most other SH3 molecules. In this variation, the molecule forms what looks like two pairs of hands clasped together.

Other SH3 molecules are made up of atoms that look like one pair of hands clasped together.

³We think that this is a very different SH3 domain than those previously studied. Now that we know what it looks like, others can hopefully discover how it works and what it could be used for,² said Newcomer.

Structural biology, besides providing a basis for understanding how the molecules communicate and function, also provides a basis for the design of new pharmaceuticals, which depends on knowledge of protein structure.

Structural biologists use both x-ray crystallography and Nuclear Magnetic Resonance Spectroscopy to define a molecules three dimensional structure.