A team including researchers from McGill University, Concordia University and the Canadian Light Source (CLS) synchrotron have used crystallography to confirm a 50-year-old hypothesis: chains of the nucleotide adenosine monophosphate (AMP) can form a double helix structure.

As long ago as 1961, Watson and Crick hypothesized that chains of AMP — known as poly(A) — could bind to each other, forming helical structures. But the theory was hard to prove because such molecules are extremely difficult to crystallize. “Lots of people have been trying,” says Kalle Gehring, a professor of biochemistry at McGill. “We came across the right conditions by accident.”

Poly(A) ‘tails’ are often added to the end of messenger RNA in eukaryotic organisms, and are bound by a protein called — what else — poly(A) binding protein. Gehring and his team were trying to study this protein in action by crystallizing it in an ammonium phosphate buffer. They sent their samples to be imaged with the high-intensity X-rays produced at CLS in Saskatchewan, but the diffraction pattern produced didn’t match to the protein. The data remained a puzzle for more than three years until the team contacted a world-leading crystallographer named George Sheldrick at the University Göttingen. Sheldrick tackled the problem with sophisticated software and supercomputers and, after a week of processing, the image of a double helix made of two strands of poly(A) emerged. 

The structure is strange in that it features A-A binding (A normally pairs with T in DNA and or U in RNA) and, unlike the two anti-parallel strands of DNA, both halves of the poly(A) double helix run in the same direction. Moreover, because ammonium ions appear to be required for its stabilization, the A-A bonding can be ‘switched’ on and off by controlling their concentration. This could be a boon to supermolecular chemists using DNA to build nano-structured materials for drug delivery and other applications. “It’s another gadget in their tool chest,” says Gehring. 

Short chains of adenosine monophosphate (AMP) – a nucleotide base for both DNA and RNA – can form the double helix shown above (the grey spheres represent ammonium ions.) Unlike­ DNA, the strands of this helix are parallel­ and formed of A-A base pairs. Photo credit: Kathryn Janzen, Canadian Light Source