A 3-D image reveals a steroid-gene link.
Steroids alter the rate of protein production in the body by relying on a separate receptor molecule to find the target gene. In the Aug. 8 Nature, Paul B. Sigler of Yale University and his co-workers show how a gene fragment binds to the part of a steroid receptor that recognizes specific DNA sequences. Their three-dimensional, computer-generated image, based on X-ray crystallography, reveals that it is not only the binding between DNA and the steroid-receptor molecule, but also the spacing between binding regions, that tells these gene-activating molecules when they've latched onto the right gene.
Working with Leonard P. Freedman of the Sloan-Kettering Institute in New York City and Keith R. Yamamoto of the University of California, San Francisco, Sigler's team began by modifying the gene fragment: They added an extra unit of DNA, called a base pair, to the middle of its, 15-base-pair sequence. Next they synthesized lots of the modified fragment and made multiple copies of the receptor segment that recognized this specific gene fragment.
When one receptor segment latches onto the first six base pairs of the gene fragment, the segment slightly alters its structure, thereby making it easy for a second segment to link with it - forming what is called a dimer. That second segment twists around to home in on the fragment's last six base pairs, whose sequence represents a symmetrical version of the first six. But with the extra base pair in between - making it four instead of three - the dimer fails to line up well with the DNA, so recognition is poor, says Sigler.
When his team repeated the work with unmodified gene fragments, they found that the segments did bind tightly to the DNA. This indicates that the three base pairs in between those that combine with the dimer create the correct spacing that lets the steroid receptor know it has found its target gene, Sigler says.
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|Title Annotation:||three-dimensional, computer-generated image reveals how steroid hormones turn on genes|
|Date:||Aug 10, 1991|
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