Rice University scientists have created a way to interpret interactions among pairs of task-oriented proteins that relay signals. The goal is to learn how the proteins avoid crosstalk and whether they can be tuned for better performance.
Each cell contains thousands of these two-component signaling proteins, which often act as sensors and trigger the cell to act.
The new research has significance for bioengineers who try to understand and modify signaling pathways to treat disease or carry out tasks. A paper on the research done at the Center for Theoretical Biological Physics (CTBP) at Rice's BioScience Research Collaborative appears online this month in the Proceedings of the National Academy of Sciences.
The research team led by Rice physicist Jos Onuchic and bioengineer Herbert Levine used the predictive power of their pioneering direct coupling analysis statistical method to compare the genomic roots of thousands of protein pairs collected from many different bacterial organisms. Their product is a new metric to judge how mutations affect the way the pairs work.
Two-component systems are usually disconnected proteins that transmit signals to trigger many types of actions within cells. In bacteria, for instance, the first component is a histidine kinase (HK) that senses conditions outside a cell and triggers the creation of a signal in a process called "autophosphorylation." The signal (that is, the phosphoryl group) generated on the kinase can then be passed to a response regulator (RR) protein, akin to a baton in a relay race. The regulator takes the baton and then generates a physiological response through the activation or repression of genes.
A central question for the researchers was how these kinases and regulators coevolve to recognize each other in a crowd, and why there's so little crosstalk leading to mismatched pairs.
"If we are going to figure out how cells are able to compute, we
|Contact: David Ruth|