Scientists uncover new way adenosine interacts
By Aline McKenzie
Every living creature depends heavily on a molecule called adenosine triphosphate, or ATP. Like a locomotive pulling three boxcars, it consists of a compound called adenosine that drags three chemical groups called phosphates behind it.
|Dr. Kim Orth (right) and graduate student Melanie Yarbrough found a biochemical process so novel they had to create a name for it.|
As one of its major functions, ATP alters the functions of enzymes and other molecules. It does this by allowing its “caboose” phosphate group to break off and attach to the other molecules, changing their shape and, consequently, how they act.
Researchers at UT Southwestern have found a completely new way that ATP can alter another molecule: by breaking off the “locomotive” adenosine and the first phosphate group and attaching them to a tar get.
“It was a surprise that you could use the other end of the ATP molecule like this,” said Melanie Yarbrough, graduate student in molecular microbiology and first author of a study in Science that describes the process.
The process is so novel that the researchers created a new name for it: AMPylation, where AMP stands for adenosine monophosphate.
In addition, they found that AMPylation is involved in the death of cells infected by Vibrio parahaemolyticus, a bacterium that causes food poisoning via the consumption of contaminated shellfish.
The culprit from the bacterium is a virulence factor called VopS, a protein previously known to cause infected cells to collapse and die.
Using radioactively labeled ATP mixed with human and Vibrio proteins, the researchers found that VopS attaches AMP to a group of proteins called Rho GTPases.
Rho GTPases are known to help maintain the framework of cells. When modified by AMP, they are unable to function properly, causing the cells to collapse and die.
“We knew VopS was important for the pathogenesis of Vibrio, but we didn’t know what it was doing,” Ms. Yarbrough said.
The researchers also found that the process is common in both bacteria and human cells.
“The enzyme that performs this modification is found in eukaryotes and prokaryotes,” said Dr. Kim Orth, associate professor of molecular biology and senior author of the paper.
Other UT Southwestern researchers involved with the study were Dr. Yan Li, assistant professor of internal medicine; Dr. Lisa Kinch, bioinformatics research scientist; Dr. Nick Grishin, associate professor of biochemistry; and Dr. Haydn Ball, assistant professor of internal medicine.