Molecular Structure of Key Enzyme Solved

Release Date:
4/2/2002
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"If any enzyme does the cell's heavy lifting, it's RNA polymerase II," begins a recent scientific news article. (1) RNA polymerase II is responsible for the first step in making proteins in all organisms ranging from yeast to humans. The multisubunit enzyme copies each cell's genes into RNA, a type of genetic material that serves as an intermediary between genes and proteins. And it does this at just the right time and in just the right amounts. The article continues, "pol II, as the enzyme is called, is the heart of the machinery that controls everything that cells do--from differentiating into all the tissues of a developing embryo to responding to everyday stresses."

A group of researchers led by Dr. Roger Kornberg of the Stanford University School of Medicine has solved two detailed, three-dimensional structures of pol II--one of the enzyme alone and one with the enzyme joined to some of its molecular partners. The feat culminates nearly 20 years of effort. It is particularly remarkable because the enzyme is rather scarce in cells and is so large--it contains 12 different subunits--that it is unwieldy for the required technique (X-ray crystallography).

The solved structure gives scientists their first close look at the enzyme in action. It suggests a role for each of the enzyme's dozen subunits and reveals how they fit together to form a molecular machine that copies genes into RNA. The work may have clinical applications as well. Researchers may be able to design new antibiotic drugs by targeting structural differences between human and bacterial forms of the enzyme. They may also be able to design anticancer drugs that prevent pol II from stimulating cell growth in tumor cells.

RNA 1 Graphic

The structure of RNA polymerase II shows, at the molecular level, how the enzyme completes the first step in making proteins--copying genes into RNA. It reveals a pair of jaws that appear to grip genes (DNA), a clamp that holds the DNA in place, a pore through which RNA building blocks probably enter, and grooves through which the completed RNA strand may thread out of the enzyme.

REFERENCES

1 Marx J. X-ray crystallography: transcription enzyme structure solved. Science 2001; 292: 411-4.

Cramer P, Bushnell DA, Kornberg RD. Structural basis of transcription: RNA polymerase II at 2.8 angstrom resolution. Science 292:1863-76, 2001.

Gnatt AL, Cramer P, Fu J, Bushnell DA, Kornberg RD. Structural basis of transcription: An RNA polymerase II elongation complex at 3.3 angstrom resolution. Science 292:1876-82, 2001.

Klug A. Structural biology: A marvelous machine for making messages. Science 292:1844-6, 2001. (in Perspectives)

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