It is not often that a brand new protein arises out of evolution. Moreover, if such a protein is born, how might it begin to fold into its three-dimensional structure? A team from the University of Arizona finds this example in yeast and describes their first glimpse in understanding the structure of new, de novo proteins.
The team has identified a gene called Bsc4 in Saccharomyces cerevisiae that has naturally evolved from a previously segment of noncoding, junk DNA. From expression and purification in E. coli, the team has been able to make some general information about the resulting protein's shape and structure. They find that instead of existing as monomers, Bsc4 forms compact oligomers of varying stoichiometries.
"Most natural proteins exist in a certain size," says senior author Matthew Cordes. "This one can be in groups of four, five, six, seven—that's one reason you might call the structure fuzzy or rudimentary."
The protein has some characteristics of normal proteins, such as the formation of secondary structures. In particular Bsc4 appears to form compact oligomers with high beta sheet content and a hydrophobic core. It is also susceptible to unfolding under high temperatures and in the presence of the guanidine chemical denaturant. Surprisingly, in its oligomer form, Bsc4 appears offer some resistance to thermal denaturation.
Bsc4 exhibits affinity for special dyes that are known for binding to oligomeric amyloid intermediates, suggesting a structure that is not fully defined or globular. Cordes calls this structure, "molten globular" because it may shift between different shapes.
"What we've discovered doesn't come across as a completely developed biological molecule. It looks like what you'd think a newborn protein would look like—maybe a little clumsy or hazily formed," said Cordes. "But nonetheless, this protein folds into a three-dimensional structure and by a lot of measures it looks like proteins that evolved long ago.”
In the team’s recent publication in Cell Structure, the authors conclude that even evolutionarily young de novo proteins can demonstrate structural order and native-like properties.
Image: BSC4 is a young de novo gene, arising from a previously non-coding region of the S. cerevisiae genome. Like older genes, its encoded protein has an ability to fold, but has unusual properties. Image courtesy of Elsevier / Cell Structure / Matthew Cordes.