Resurrected 4-Billion-Year-Old Protein Reveals Clues to Evolution of Shape

Proteins today possess an impressive degree of structural diversity. Yet exactly how these shapes evolved has long remained a mystery. Now, scientists are unraveling exactly how these 3D structures arose by resurrecting a 4-billion-year-old Precambrian protein in the laboratory.

"So far, attempts to understand protein structure evolution have been based on the comparison between structures of modern proteins. This is equivalent to trying to understand the evolution of birds by comparing several living birds," said Jose Sanchez-Ruiz of the University of Granada in a news release. "But it is most useful to study fossils so that changes over evolutionary time are apparent. Our approach comes as close as possible to 'digging up' fossil protein structures."

In order to get a better glimpse of the evolutionary history of protein structures, the researchers constructed a phylogenetic tree of protein sequences by analyzing the amino acid sequences of thioredoxins--proteins found in organisms from the three domains of life. These included bacteria, archaea and eukaryotes.  Using this phylogenetic tree, the scientists were able to resureect Precambrian proteins in the laboratory and characterize their features.

The scientists then analyzed the X-ray crystal structures of the resurrected proteins. This allowed them to gain novel insights into protein evolution. More specifically, they found that present-day thioredoxin structures are remarkably similar to those that existed at a time close to the origin of life, even though their amino acid sequences are very different.

"In addition to uncovering the basic principles of protein structure evolution, our approach will provide invaluable information regarding how the 3D structure of a protein is encoded by its amino acid sequence," said Sanchez-Ruiz in a news release. "It could also provide information about how to design proteins with novel structures--an important goal in protein engineering and biotechnology."

The findings are important for understand the evolutionary history of proteins. In addition, it can lend further insight into the future structures and, potentially, modifying proteins for our own use.

The findings are published in the journal Structure.