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New molecular structure offers first picture of a protein family vital to human health
Date:5/31/2012

The 20 proteins in the Wnt family are some of the most important proteins in controlling how an organism develops and grows, but for 30 years scientists have not known what these vital proteins actually look like. The proteins have eluded standard visualization techniques, in large part because they do not dissolve well in the water-based liquids normally used for biochemical studies. But once Howard Hughes Medical Institute investigator K. Christopher Garcia, and Claudia Janda, a post-doctoral fellow in his Stanford University School of Medicine lab, thought of an approach to make the proteins behave better, they succeeded in solving the first structure of a Wnt protein.

Their work, published June 1, 2012, in the journal Science, reveals an unexpected three-dimensional shape that offers clues to how Wnt proteins function and clarifies the nature of its Frizzled receptor target for drug developers working to design anti-Wnt therapies for cancer and other diseases. "Having finally gained structural access to Wnts, I think this is going to open up a whole new era in molecularly dissecting the role of Wnt proteins in biological processes," says Garcia.

Wnt proteins were discovered 30 years ago by Harold Varmus, the current director of the National Cancer Institute, and Roel Nusse, who is now an HHMI investigator at Stanford University. They observed that Wnt1, the gene for a Wnt protein, was very active in breast cancer cells from mice. Over the past decades, researchers have shown that Wnt proteins play key roles in embryonic development, tissue regeneration, bone growth, stem cell differentiation, as well as many human cancers. In essence, Wnt proteins help give cells their identity and tell them how to behave.

"This is one of the most important ligand-receptor systems in both human and invertebrate biology. Wnts cut across every field, which is why I got involved. But many excellent groups have tried to express them in the lab a
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
Source:Eurekalert

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