Biochem 911: USU Scientists Explore Protein Structure and Function
Thursday, Aug. 25, 2011
L to R, Joanie Hevel, Sean Johnson and Laurel Gui study the structure and function of proteins. Gui, lead author on a paper the team published in 'Journal of Biological Chemistry,' was named a 2011 American Heart Association Predoctoral Fellow.
Structures highlighted in color on a model of PRMT1 reveal the 'business end' of the protein. Specific amino acids, shown in red, function as ‘molecular tweezers’ that are critical for proper control of the protein’s product formation.
To ensure your survival, every single cell in your body is equipped to quickly adapt to forces outside of it, says Utah State University biochemist Joanie Hevel.
“When you’re hungry or too full, tired or in pain, your cells immediately jump into action in a complex series of interactions,” says Hevel, associate professor of biochemistry in USU’s Department of Chemistry and Biochemistry. “The way your cells interact and regulate biochemical functions is through catalysts known as enzymes, most of which are proteins.”
Hevel likens interactions between cells and enzymes to the flow of information that occurs during a medical emergency.
“An accident happens, someone is injured, someone else calls ‘911’ and an operator responds and dispatches help,” she says. “In a similar way, proteins receive a ‘distress’ signal from a cell and initiate an intricate web of biochemical relays.”
Most proteins are thought to perform just one function but Hevel and her team are studying an intriguing enzyme called PRMT1 (Protein Arginine Methyltransferase I) that produces not one but two forms of an amino acid with completely different functions. With USU doctoral student Laurel Gui, Hevel and faculty colleague Sean Johnson, R. Gaurth Hansen associate professor of biochemistry, along with recent USU undergrad research intern Paula Porter published their findings in the August 19, 2011, issue of the Journal of Biological Chemistry.
“When an enzyme can produce two products and each product has different biological functions, how does the enzyme control which product to make?” asks Gui, the paper’s lead author who was recently named an American Heart Association Predoctoral Fellow.
Hevel, who has long studied protein functions, enlisted the help of Johnson, who uses x-ray crystallography techniques in combination with biochemical analysis to understand the structure and mechanism of proteins, to aid the research team’s efforts.
“To understand a protein’s functions, you need to understand its structure,” Hevel says. “When a protein isn’t functioning properly, bad things happen in the cell.”
Release of too much or too little of a protein’s products can lead to cardiovascular disease, disrupt the cell’s ability to defend itself from a pathogen, lead to cancer or possibly cause neurological dysfunction.
“Understanding how proteins work is essential to the design of drugs to treat disease,” Hevel says. “Most drugs are either inhibitors that suppress a faulty enzyme or activators that increase a lagging protein’s function.”
To understand PRMT1, the USU team examined the protein piece by piece.
“We found specific amino acids functioned as ‘molecular tweezers’ to guide modification of targeted proteins, thereby modulating the information that’s communicated to the cell,” says Johnson, a 2010 grant recipient of the National Science Foundation’s Faculty Early Career Development (CAREER) program.
The team’s discovery offers critical insight into how PRMT1 and similar proteins are engineered, Hevel says.
“When you get into the protein’s innards, you learn a lot about its function,” she says. “That can really affect our ability to control the message each cell receives and how it reacts.”
Contact: Joanie Hevel, 435-797-1622, firstname.lastname@example.org
Contact: Sean Johnson, 435-797-2089, email@example.com
Writer: Mary-Ann Muffoletto, 435-797-3517, firstname.lastname@example.org