The Transformers cartoons are full of characters that gain new abilities by changing shape, turning from vehicles into robots with incredible speed. Now, scientists have found a protein in the humble gut bacterium, Escherichia coli, that uses a similar shape-shifting trick: according to a study published today in Cell, the RfaH protein quickly converts from one form that guides transcription to another involved in translation—the two key steps of protein production. Without RfaH’s transformation, the bacteria would be unable to complete the process from DNA to protein for many of their genes.

“It’s a highly significant finding, and one of the most dramatic shifts in a protein structure reported,” said Max Gottesman, a biochemist at Columbia University who was not involved in the research.

Irina Artsimovitch from Ohio State University started working on RfaH in 2000. Based on its sequence, she assumed that it would have the...

Together with Paul Rösch’s group at the University of Bayreuth, Artsimovitch’s team discovered that RfaH consists of two halves, which are usually held in close contact and linked by a thin thread of amino acids. One half folds into an alpha form, which resembles a pair of nunchucks, while the other sticks to RNA polymerase, the enzyme that transcribes DNA into RNA. RfaH prevents the polymerase from stalling, and allows it to read an entire gene.

When RfaH binds to a polymerase, that half releases the alpha form, which completely refolds into the beta-barrel resembling a flower. In this form, it recruits passing ribosomes. Without this switch, around 10 percent of E.coli’s RNA would never be translated into proteins.

A few other proteins can change shape, but none do so to such a dramatic extent, noted Bjorn Burmann from the University of Bayreuth, Germany [affiliation with study?]. Indeed, not only does the gross shape of the protein change dramatically, but “it turns inside out,” said  Artsimovitch. On changing into the beta-barrel, “the [amino acids] that were on the surface are now in the center.”

For now, the team has no idea how the protein refolds, but Artsimovich said that it “happens spontaneously and very fast.” If the two halves of RfaH are severed, the alpha form quickly transforms. Even changing a single amino acid can trigger the switch. “It’s not the model you would naturally propose because it’s so wild,” Artsimovich she said.

However, Vijay Pande, a chemist and structural biologist at Stanford University said that people who work on proteins are used to the idea that small tweaks to the sequence of amino acids can greatly change the folding pattern. “I don't think people in the field would be shocked by this, but it’s a really cool example,” he said. C. Robert Matthews, a biochemist from the University of Massachussetts Medical School added, “Proteins are relatively fragile entities whose structures and functions are susceptible to subtle changes in their sequences or environments. RfaH provides a remarkable example of this sensitivity.”

It is unclear if RfaH is unique in the scale of its transformation, but Artsimovich suggests that prions—infectious proteins known to cause several brain diseases—may behave in the same way. Prions transform from a harmless default shape into a different harmful one, a transition that might be governed by a similar alpha–beta conversion as happens with RpaH.

“I expect that other proteins could do something as dramatic because if one can do it, why not others?” says Artsimovich. “You just need to show that it can happen and then people will look for other examples.” RfaH is part of a large family of proteins that control transcription in all living things, and the other members of this dynasty may be a good place to start looking for more dramatic transformers.

“I think it is very exciting to see if this is potentially a general paradigm or just an unusual minority case,” Pande said.

B. Burmann, et al., “An alpha Helix to beta Barrel Domain Switch Transforms the Transcription Factor RfaH into a Translation Factor,” Cell, doi:10.1016/j.cell.2012.05.042

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