DNA is remarkably supple — it can be bent, twisted, stretched or squashed into any number of different shapes. The classical, right-handed double helix (pictured right), with 10.4 bases per turn and a phosphate-phosphate distance of roughly 7 Å, is known as B-form DNA. Other stable DNA variants include the A-form structure, in which the distance between phosphate groups is nearer to 5.9 Å, and Z-form DNA, which has a left-handed conformation.

Reporting in Proceedings of the National Academy of Sciences (95, 14152-14157; 1998), Jean-François Allemand and colleagues now describe how, through a clever piece of molecular yoga, they have identified another stable DNA conformation. Christened P-form DNA (far right), this new structure is 75% longer than the B form, with just 2.62 bases per turn. Most surprisingly, the phosphate backbone (purple) — which, in B-form DNA wraps around the bases (yellow and blue) — is on the inside.

Allemand et al. attached one end of a DNA strand to a flat surface, and the other to a magnetic bead. Then, using magnets to control the position of the bead, they stretched and twisted the DNA. When a force of 3 pN was applied to a positively supercoiled molecule, some of the DNA adopted the new, P-form structure. Such a structure may form in vivo too, as the authors believe that these conditions could be re-created during replication and transcription.

A P-DNA-like structure has been found in the genome of the Pf1 virus. Moreover, just a few months before Watson and Crick published their famous description of DNA, Linus Pauling and Robert B. Corey proposed another structure for nucleic acids (Proc. Natl Acad. Sci. 39, 84-97; 1953). Like Allemand et al., Pauling and Corey believed that the “core of the molecule is probably formed of [the] phosphate groups”. But although we now know DNA inside-out, it is unlikely that this will be the last new conformation to be discovered.