Aaron Klug

Medical Research Council

Election Year: 1984
Primary Section: 22, Cellular and Developmental Biology
Secondary Section: 21, Biochemistry
Membership Type: Foreign Associate

Research Interests

My research has been concerned with the interactions between proteins and nucleic acids in a number of specific systems. My first work was on the structure of simple viruses, particularly on the structure and assembly of Tobacco Mosaic virus. We found that the helical particle assembled in an ordered manner, beginning with a two-layer protein disk, which fulfilled the physical requirement for nucleating the assembly and the biological requirement for specific recognition of the RNA. The structure of the disk of molecular weight of 600,000, solved to high resolution, together with parallel biochemical studies, led to a detailed proposal for the initiation process. My next major work was on chromatin where we solved the structure of the nucleosome core particle by x-ray crystallography and the arrangement of nucleosomes to form the next level of structure by electron microscopy. In the course of this work, we showed that the fifth histone, H1, mediated the folding of the nucleosomes into the higher order structure. During these studies of viruses and chromatin, I developed a method of obtaining the three-dimensional structure from a series of tilted specimens in the electron microscope crystallography. In the last ten years, my attention has shifted from the nucleosome and chromatin to the study of transcription factor binding to DNA. This led to the discovery of the zinc finger, an independently folded protein module which is used to build up domains for recognizing DNA. Very recently, we have used the zinc finger design to engineer a novel protein which has been shown to be effective in switching off a deleterious gene in a cell line. My other current interest is in RNA enzymes, ribozymes, the structure of one of which has just been solved in my laboratory.

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