Another Kornberg Nabs A Nobel

Roger D. Kornberg, a structural biologist at Stanford University, has been awarded the 2006 Nobel Prize in Chemistry for his studies on the molecular basis of eukaryotic transcription, the process by which the genetic code of DNA is converted into messenger RNA for later translation into proteins.

Kornberg is following in his father's footsteps. Arthur Kornberg, a biochemist at Stanford, received the Nobel Prize in Physiology or Medicine in 1959 for his work on DNA replication. The younger Kornberg will receive his Nobel Prize, worth more than $1.3 million, at a ceremony in Stockholm in December.

"Roger Kornberg has made fundamental contributions to the biochemistry and structural biology of eukaryotic transcription," says Seth A. Darst, a structural biologist at Rockefeller University. "His work, ranging from chromatin structure and its effects on transcription regulation, to the complicated machinery eukaryotic cells use to regulate transcription activation, to the detailed chemistry and structural biology of the transcriptional enzyme itself, is characterized simultaneously by its breadth as well as its depth."

Kornberg has used the yeast Saccharomyces cerevisiae as a model eukaryotic organism. He developed an in vitro yeast transcription system that contained highly purified RNA polymerase II and five helper proteins known as general transcription factors. However, the system did not respond to the addition of other transcription factors known to activate specific genes in cells. This observation led Kornberg to discover a protein complex known as Mediator, which serves to transfer signals from gene-specific transcription factors to RNA polymerase II and the general transcription factors.

In 2001, Kornberg and his colleagues published high-resolution X-ray crystal structures of a 10-subunit yeast RNA polymerase and of a complex consisting of RNA polymerase, template DNA, and product RNA (Science 2001, 292, 1863 and 1876). These structures showed that the two largest subunits of RNA polymerase lie in the center on either side of a nucleic acid-binding cleft, with the smaller subunits on the outside. The cleft is bridged by an ??-helix that acts like a ratchet to move the growing RNA transcript out of the active site during RNA synthesis.

The RNA polymerase machinery "is the largest and most complex nonrepetitive protein structure reported to date," says Phillip A. Sharp, professor of biology at Massachusetts Institute of Technology and 1993 Nobel Laureate in Physiology or Medicine. "This work sets a standard for future studies of large protein complexes, which we now realize are critical in gene regulation."

Since 2001, Kornberg's lab has solved crystal structures of RNA polymerase in different functional complexes with DNA, RNA, nucleotides, or other proteins. These structures combine to give a more detailed picture of the molecular processes underlying transcription.

His team continues to work on two "grand challenges," Kornberg said in a telephone press conference. The first is a structure of RNA polymerase with the five general transcription factors, and the second is the structure of Mediator. "Work is progressing, but we still have a ways to go," he said.