[excerpt] One by one, they slightly "mutated" the normal arrangement of atoms in proteins to effectively delete hydrogen bonds at five analogous positions along the structural "backbones" of two different protein molecules that fold in the same pattern. Then they analyzed how each deletion affected the stability of the protein. "Stability" means how low energy, or "relaxed," the protein was.
"We deleted each hydrogen bond and then measured how relaxed the protein was afterwards," Fitzgerald said. "It turns out we destabilized the structure in each case. So the relaxed state was not so relaxed any more. The proteins were more stable with those hydrogen bonds.
"Those bonds seemed to clearly play a role in protein folding. And what we were able to uncover in this work is that this role may be highly conserved in a protein fold."
With Wang as the first author, the three chemists described their results in a paper published online on Friday, Feb. 10, 2006 in the journal Proceedings of the National Academy of Sciences. Their research was funded by the National Institutes of Health.
Their paper reported that deletions at each position on one folded protein, known as Arc, had the identical effect at the analogous position on the other protein, called CopG. "Remarkably, the five paired analogs with...mutations at structurally equivalent positions were destabilized to exactly the same degree," the authors wrote.
Obtaining equivalent results in five different places on two different molecules suggests that the thermodynamics, or energy, of such hydrogen bonding interactions "are conserved in a protein fold," their paper added. The word "conserved" means that those could be fundamental features of the folding state, Fitzgerald said.
The Proceedings of the National Academy of Sciences paper also notes that "the generality of our results to other protein folds remains to be explored. However, the results of our studies on Arc and CopG suggest that the conservation of backbone hydrogen-bond thermodynamics in a protein fold may be an important general principle of protein folding reactions."
Read the full story.
