Our life depends on molecular machinery that is continuously at work in our bodies. The structure of these nanometre-scale machines is thus at the heart of our understanding of health and disease. This is very apparent in the case of the Watson-Crick DNA double-helix structure, which has been the key to understanding how genetic information is stored and passed on.
An image of the DNA double helix structure taken with the AFM, with the Watson-Crick DNA structure overlaid (purple and blue).
Watson and Crick’s discovery was based on diffraction of X-rays by millions of ordered and aligned DNA molecules. This method is extremely powerful and still used today – in a more evolved form – to determine the structure of biological molecules. It has the important drawbacks, however, that it only provides static, averaged pictures of molecular structures and that it relies on the accurate ordering and alignment of many molecules. This process, called crystallisation, can prove very challenging.
To demonstrate the power of their method, Pyne, Hoogenboom and collaborators have measured the structure of a single DNA molecule, finding on average good agreement with the structure as it has been known since Watson and Crick. Strikingly, however, the single-molecule images also reveal significant variations in the depths of grooves in the double helix structure.
While the origin of the observed variations is not yet fully understood, it is known that these grooves act as keyways for proteins (molecular keys) that determine to which extent a gene is expressed in a living cell. The observation of variations in these keyways may thus help us to determine the mechanisms by which living cells promote and suppress the use of genetic information stored in their DNA.