The Secret Life of Proteins
Perspectives On Line: The Magazine of the College of Agriculture and Life Sciences

NC State University

Spring 2002 Contents Page Features Workable Solutions Man With a Plan LEAP into the ClassroomWhen Roundup Ready Cotton Isn't Ready for Roundup

An Enlightening Conversation

Biotechnology and Humanity The Secret Life of Proteins College Profile Noteworthy News Alumni Giving Items of Interest From the Dean College of Agriculture & Life Sciences  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Mattos is currently studying a gene and its protein thought to play an integral role in the development of perhaps 30 percent of human cancers.  (Photo by Herman Lankford)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

"The Secret Life of Proteins" by Dave Caldwell: The X-Ray Crystallography Laboratory gives faculty a tool to discern the structure of proteins.

 

Dr. Carla Mattos (left) works in the X-ray Crystallography Laboratory, which is likely to be important to the College's research thrust in proteomics, the study of the structure and operation of proteins.  (Photo by Herman Lankford)

ornate letter Even Superman would be envious of the X-ray “vision” to which College of Agriculture and Life Sciences faculty members have access.

With the development of the X-ray Crystallography Laboratory, faculty members have the ability to discern life at its most basic level, a three-dimensional view of the atomic structure of molecules.

The lab was established in 1999 in Polk Hall. That’s the same year that Dr. Carla Mattos, assistant professor of biochemistry, joined the faculty. Mattos is an X-ray crystallographer.

X-ray crystallography is a powerful tool in studying the structure of proteins, says Mattos. The technology gives scientists the ability to determine the three-dimensional arrangement of atoms in a protein molecule and to better understand how proteins function.

An understanding of the structure and operation of proteins is an integral element in understanding how life functions and malfunctions. Proteins, after all, do much of the work of living. Genes contain instructions for the formation of various proteins, and the proteins perform many of the tasks that allow an organism to function. By the same token, genetic defects can produce proteins that do not function correctly, leading to various diseases.

Indeed, proteomics, the study of the structure and function of proteins, is seen by many in the scientific community as an increasingly important discipline and, with genomics, is an area of emphasis in the College.

The X-ray Crystallography Lab is likely to be an important element in the College’s proteomics thrust, says Dr. Dennis Brown, head of the Department of Molecular and Structural Biochemistry. The lab is in Brown’s department.

Brown points out that X-ray crystallography is actually a fairly old technology. James Watson and Francis Crick used the technology in the 1950s as they worked to deter-mine the structure of the DNA molecule. The technology has enjoyed something of a renaissance in recent years as more sophisticated computer programs and faster computers have become available, Brown says. More powerful computers are better able to interpret the data that X-ray crystallography provides.

X-ray crystallography takes advantage of the relatively short wavelength of X-rays to produce images at the atomic level, Mattos explains. If an object is to be seen, its size must be at least half the wavelength of the light used to see it. That’s why it’s impossible to obtain atomic resolution through even the most powerful light micro-scope. The wavelength of light is much larger than the distance between atoms in a molecule.

The wavelength of an X-ray, on the other hand, is short enough to reveal atoms. But there’s no known way to focus X-rays, so X-ray crystallography doesn’t work the same way a microscope does.

Molecules to be studied must first be arranged in a crystal lattice, which means every molecule has the same orientation, says Mattos. X-rays are then beamed onto the crystal, which diffracts the X-rays according to the position of atoms in the molecule. This diffraction pattern is then interpreted to determine the three-dimensional structure of the molecule. The technology has become more valuable in recent years as more powerful computers have been used to interpret diffraction patterns and produce three-dimensional images of proteins.

Molecules are crystallized by putting them in various solutions composed of salts and organic solvents. Different molecules respond to different solutions.

Says Mattos, “There’s actually quite a lot of time spent screening solutions.”

The result is an image that can give scientists insights into how a protein functions. Mattos, for example, is studying a protein known as ras. It is produced by a gene that goes by the same name. The ras gene and its protein are thought to play an integral role in the development of perhaps 30 percent of human cancers.

The ras protein is a messenger, Mattos explains. It receives signals that originate outside a cell and transmits them to other signaling proteins within the cell that ultimately control the activation and deactivation of the cell’s reproductive machinery. Normally, the ras protein is constantly activating and deactivating, switching a cell’s reproductive machinery on and off in response to the appropriate stimuli.

But if a mutation occurs in the gene that produces the ras protein, a defective ras protein can result. The protein’s deactivation mechanism breaks down and the cell multiplies uncontrollably, becoming cancerous.

Mattos is using X-ray crystallography to look at the surface of the ras protein to better understand how the protein binds itself to cells and other proteins.

“We’re trying to understand the changes in the mutant protein so we can inhibit its deleterious actions,” says Mattos.

The technology can be used to study a range of other proteins that perform a variety of tasks. Because the X-ray Crystallography Lab is still relatively new, it is not heavily used yet. But Mattos says faculty and students are rapidly discovering the lab and its potential to aid them in revealing the secrets of proteins.


 


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