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

May 28, 2025 | 08:00pm

Rare ‘ambidextrous’ protein breaks rules of handedness

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

The ‘helix-hairpin-helix’ motif allows a peptide to bind to both DNA and its mirror image.Credit: Liam M. Longo

Scientists have discovered an ancient protein that has the rare property of being ‘ambidextrous’ — it can function in mirror-image forms. The molecule could be a relic of a time when life based on mirror-image molecules existed on Earth.

Many chemicals have a handedness, or chirality, and can exist in two mirror-image forms. But the building blocks of life tend to stick to one or the other. Sugars in nucleic acids such as DNA are right-handed — causing the DNA double helix to twist to the right, if you were looking down its axis — whereas the amino acids that build proteins are left-handed.

Scientists think that a preference for right-handed DNA and left-handed proteins could have helped to maintain the stability and function of biomolecules early in life’s evolution.

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

The symmetrical segment — called a helix-hairpin-helix motif — is common in proteins that can manipulate and bind DNA and RNA and is found across the tree of life, suggesting that it existed in an early ancestor of all cells, says Longo.

Forwards, backwards, this way, that way

To test his hunch about the molecule’s ambidexterity, Longo and his colleagues created ‘right-handed’ versions of the peptide, including an ‘ancestral’ form potentially similar to the one found in the last universal common ancestor (LUCA) of today’s cells.

The mirror-image peptides bound to DNA nearly as well as their twins, and normal, left-handed versions were able to bind mirror-image DNA. Further experiments showed that both left- and right-handed versions grabbed DNA molecules in similar ways. A study describing the phenomenon is published¹ in Angewandte Chemie.