A rare "ambidexter" protein violates the rules of the hand

Most proteins are left-handed, but scientists have found an ancient molecule that works in both mirror forms.

Scientists have discovered an ancient protein that has a rare "ambidextral" property - it can function in mirror forms. The molecule may be a relic of time when there was life on Earth based on mirror reflection molecules.

Many chemicals have chirality and can exist in two mirror forms. But the building blocks of life, as a rule, stick to one or the other. Sugars in nucleic acids, such as DNA, are right, which causes the double helix of DNA to twist to the right if you look down its axis, while the amino acids that create proteins are left.

Scientists believe that preferring right DNA and left-handed proteins could help maintain the stability and function of biomolecules in the early evolution of life.

Liam Longo, a protein historian at the Tokyo Institute of Earth and Life Sciences, studied a protein fragment, or peptide, that recognizes nucleic acids and is commonly found in enzymes to restore DNA. He noticed that the structure was symmetrical around the central axis, and suspected that both the left-handed and right-handed versions of the protein could bind to DNA.

A symmetrical segment called the spiral-hair-spiral motif is common in proteins that can manipulate and bind DNA and RNA, and occurs through the tree of life, which suggests that it existed in the early ancestors of all cells, says Longo.

Forward, backward, this way, that way

To test their premonition about the ambidexterity of the molecule, Longo and his colleagues created "right" versions of the peptide, including an "ancestral" form, potentially similar to that found in the last universal common ancestor (LUCA) of modern cells.

Mirror peptides bound to DNA in almost the same way as their twins, and ordinary left-handed versions were able to bind mirror DNA. Further experiments showed that both the left-handed and right-handed versions captured DNA molecules in a similar way. The study describing this phenomenon was published1 in Angewandte Chemie.

Why the protein structure of ambidextron is far from clear, says Longo. The most likely reason is that the motif evolved to bind DNA in multiple conformations, and ambidexterity is a consequence of this flexibility.

"There is also a crazy explanation," says Longo. The motif could have developed when there was a "mirror life" on Earth containing left-handed nucleic acids and right-hand proteins. "It would completely change what we think about the ecology of the times before LUCA. It's some kind of wild thing," he adds. If ambidexterity is a common feature of other ancient proteins that bind DNA and RNA, this may support the idea.

"This is not an unfounded hypothesis," says Michael Kay, a peptide-protein biochemist at the University of Utah in Salt Lake City, but it will be difficult to find supporting evidence.

Kay believes that the universal nature of the motif - it recognizes the chemical signatures found in both the left and right DNA - explains its ambidexterity. In 2014, the Kay team described another ambidexter protein: one that recognizes hundreds of other proteins and helps them to form properly.

Regardless of whether there was a mirror life in the Earth's past, it may be a feature of future cells. Last year, a group of scientists identified the potential risks of creating a mirror life, an aspiration that, according to them, was at least a decade3. Ambidextrous molecular features, such as the spiral-hair-spiral motif, can serve as a bridge between natural and mirror biology, adds Longo. "We are on the way to a collision with mirror life."