Posted by Lauren Rugani on March 31, 2009
New research out of UPenn School of Medicine marks the first time a protein has been built from scratch, which could open doors toward fighting diseases or creating artificial blood for use in emergency situations.
Proteins are complex structures made up of amino acids. Over the course of evolution, these structures have mutated to include many branches, pockets and folds that leave scientists to decipher how – or even if – specific structural properties are related to protein function. Until now, engineers have created new proteins by altering the structures of natural proteins to code the molecules for new and different tasks, but all at the expense of stability and predictable activity.
The UPenn team discarded the idea that synthetic proteins should exactly mimic natural proteins and found that simple and straightforward designs not only allowed for a protein to carry out the desired task, but also provided insight into the relationship between specific amino acids and the roles carried out by the protein. They presented their work last week in Nature.
The artificial protein is made up of sequences containing just three amino acids (there are 22 total known amino acids in humans) that assemble into a bundle of four helical structures. Then they added a chemical group called a heme, which contains an iron atom and is responsible for binding to oxygen in the blood and carrying it to various tissues in the body. Finally, they added different amino acids to the ends of the helices to allow the columns to open and let oxygen inside while preventing water from coming in contact with the heme.
Tests showed that the man-made protein performed just as well as its natural counterpart, with one interesting exception. In natural hemoglobin, oxygen and carbon monoxide bind to the same part of a heme, and carbon monoxide usually wins, so the protein carries a dangerous poison to the rest of the body, depriving tissues of oxygen and often resulting in cell damage or death. Carbon monoxide is about 200 times as likely as oxygen to bind to a heme, so even small amounts of the gas, like from cigarette smoke or car exhaust, can be harmful. But the engineered protein is ten times more likely to bind to oxygen than to carbon monoxide or other dangerous compounds.
I’m no expert, but perhaps these and future engineered proteins could pave the way toward treatments for hemoglobin-related diseases like anemia.