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Crystallography grabs chemistry Nobel

October 4, 2006 By Katharine Sanderson This article courtesy of Nature News.

Structural determination of RNA polymerase unlocked secrets of cells.

At the age of 19 Roger Kornberg coauthored a paper with, among others, his father Arthur Kornberg and Paul Berg. This obscure paper, 'On the heterogeneity of the deoxyribonucleic acid associated with crystalline yeast cytochrome b2'1, has the extraordinary pedigree of having three Nobel laureates among its authorship. Kornberg senior won a medical Nobel in 1959 (for discovering the mechanisms behind DNA and RNA synthesis), Berg took the chemistry prize in 1980, and now Kornberg junior, too, has snapped up a Nobel Prize in Chemistry.

The award is for his work in deciphering the molecular details of transcription the process that controls the transfer of genetic information from DNA to RNA, which is then used to drive the protein-making parts of the cell.

A 12-year-old Kornberg asked for 'a week in the lab' for Christmas."
Kornberg, a professor of structural biology at Stanford University, California (where his father is an active emeritus professor), had his major breakthrough in 2001, when he solved the structure of RNA polymerase II an enzyme that helps messenger RNA take information from DNA. By exposing crystals of the polymerase, extracted from yeast, to a brilliant beam of X-rays, he was able to painstakingly determine their structure.

Big molecule, big deal

This structure has allowed scientists to unravel the atomic workings of the enzyme and how it might function in cells. "This is the largest protein-only structure ever solved," says Jesper Svejstrup, a gene-transcription researcher at Cancer Research UK, who was a postdoctoral student to Kornberg from 1993 to 1996. "To solve the structure of such a big molecule: it's a big deal," he says.

Steve Jackson, a transcription expert from Cambridge University, UK, hails Kornberg's all-encompassing style. "The approach he's taken combines biochemistry, structural biology and molecular genetics with functional studies," Jackson says. Kornberg was also clever in choosing to study cell mechanisms in yeast, which is easier to work with than mammalian cells, Jackson says.

Understanding how RNA polymerase II interacts with other proteins has provided huge insight, Jackson says. "People are very used to thinking of DNA as encoding how our cells work, but DNA is just a blueprint. RNA polymerase puts that blueprint into action."

Like father, like son

Kornberg's academic pedigree is packed full of Nobel connections. His postdoctoral studies were with Nobel laureates Aaron Klug and Francis Crick in Cambridge, where he worked on chromatin the package of DNA and protein found inside the nuclei of eukaryotic cells.

A "burning" for science was inspired in Kornberg from an early age, notes Svejstrup. He recalls a story about when a 12-year-old Kornberg was asked what he would like for Christmas: "A week in the lab," he told his father.

Judith Howard, head of chemistry at Durham University, UK, and a crystallographer, is delighted by Kornberg's prize. "It's a wonderful recognition of his work and similar studies going on elsewhere to try to understand the function of biological processes, as well as gathering beautiful but often static information," she says.

The award falls very much on the boundaries of where chemistry interacts with biology, she notes: "It's a perfect example of interdisciplinary research." Previous chemistry prizes have gone to crystallographers for work that some might perceive as being on the edges of chemistry notably Dorothy Hodgkin, who was awarded the prize in 1964 for solving biochemical structures and with whom Howard worked. The divisions between the sciences are becoming much less obvious, she says.

Those who think Kornberg could have equally won the medicine or physiology prize, like his father, could have a point, suggests Svejstrup. But the fact that Kornberg is the sole winner of the prize highlights how important the structural information he uncovered is. "At root, it's chemistry," says Treisman.

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  1. Jackson J. F., Kornberg R. D., Berg P., Rajbhandary U. L., Stuart A.& Khorana H. G. Biochim Biophys Acta., 108. 243 - 248 (1965).
  2. Cramer P., Bushnell D. A.& Kornberg R. D. et al. Science, 292. 1863 - 1876 (2001).
  3. Gnatt A. L., Gnatt A. L., Cramer P., Fu J., Bushnell D. A. & Kornberg R. D. Science, 292. 1876 - 1882 (2001).
  4. Bushnell D. A., Westover K. D. , Davis R. E.& Kornberg R. D. Science, 303. 983 - 988 (2004).


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