At first sight it seems simple enough: DNA makes RNA makes protein, and, by extension, you and me and every living thing. But this ‘central dogma of biology’, as Francis Crick famously called it, requires some stupendously complicated machinery to make it happen, and much of the last half century of research has been devoted to unravelling the apparatus that builds life. Nobel Prizes have recognized a number of the triumphs along the way, among them Watson, Crick and Wilkins‘ decipherment of the helical structure of DNA and Roger Kornberg‘s uncovering of the workings of the enzyme RNA polymerase, which turns DNA into RNA. Now, the 2009 Nobel Prize in Chemistry recognizes three people who have made major contributions to understanding the nature of the machine that translates the RNA code into protein: the ribosome.

Venki Ramakrishnan, Thomas Steitz and Ada Yonath took the view that in order to be able to understand the ribosome, we have to be able first to visualize it. Using X-ray crystallography, an imaging technique in which the diffraction patterns formed by X-rays passing through a crystal of a substance are used to piece together that crystal’s atomic structure, they independently set out to ‘solve’ the structure of the ribosome. The tasks of preparing suitable ribosomal crystals for diffraction, and of interpreting the resulting X-ray diffraction patterns from such large and unsymmetrical entities, were at first widely viewed as impossible. But in 1980 Ada Yonath, working with the ribosomes of heat-loving bacteria that she thought might be especially robust, succeeded in preparing the first useful crystals of the larger of the ribosome’s two subunits. This marked the beginning of two decades of intense activity during which better and better crystals and images were obtained, and numerous technical hurdles were overcome, culminating with the publication of high resolution structures for both subunits in 2000. Further elaboration of the ribosomal structure has followed, with these and other groups contributing to our overall picture of how this molecular factory works to assemble protein chains.

As the target of 50% of known antibiotics, the bacterial ribosome is a structure of major therapeutic importance. With antibiotic resistance on the increase, it is hoped that an understanding of precisely how antibiotics interact with the ribosome will allow the design of new antibiotics to tackle drug-resistant bacteria. Ramakrishnan, Steitz and Yonath have all imaged the molecular interactions between ribosomes and antibiotics, providing key data to help guide structure-based drug design of new antibiotics.