The Nobel Prize in Chemistry 1982.
Aaron Klug (1926- ): "for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes"
Aaron Klug won the Nobel Prize in 1982 for his work on a special technique for solving the structures of large molecules that can't be crystallized. He used it to determine the structure of the nucleosome. Here's how Klug's contribution is described in the presentation speech.
Large molecular aggregates can seldom be obtained in a form which allows structural determination by X-ray diffraction. The investigator who has been awarded with this year's Nobel Prize in chemistry, Aaron Klug, has developed a method to study the structure of molecular aggregates from biological systems. His technique is based on an ingenious combination of electron microscopy with principles taken from diffraction methods. Electron microscopy has long been used to depict the structural components of the cell, but its power of resolution is after, limited by a lack of contrast in the picture. Klug has shown that even picture; seemingly lacking in contrast may contain a large amount of structural information, which can be made available by a mathematical manipulation of the picture.Klug started working on tobacco mosaic virus in 1954 when be began a collaboration with Rosalind Franklin who had just abandoned DNA. Klug and Franklin remained close associates until she died a few years later.
With this technique, in combination with other methods of structural chemistry, Klug has inter alia investigated viruses and chromatin of the cell nucleus. His virus studies have illuminated an important biochemical principle, according to which the complicated molecular aggregates in the cell are formed spontaneously from their components. The chromatin investigations have provided clues to the structural control of the reading of the genetic message in DNA. In a long-term perspective they will undoubtedly be of crucial importance for our understanding of the nature of cancer, in which the control of the growth and division of cells by the genetic material no longer functions.
Klug solved the structure of TMV using X-ray diffraction but this proved inadequate for other large structures. In order to solve the structures of more complex viruses (e.g., bacteriophage T4) and chromatin, Klug turned to high resolution electron microscopy. He developed techniques for assembling and refining multiple images with the aid of complex computer programs. Basically, he was able to solve the three dimensional shape using multiple two dimensional images as shown in the diagram (right) from his Nobel Lecture.
Klug's work has been modified an improved over the years. Today the electron microscopic images are much better and special low temperature electron microscopes (cryo-EM) can be used to obain images from material that would be destroyed at normal temperature. The enormous increase in computing power and modern software have led to the solution of many complex structures such as the pyruvate dehydrogenase complex.