ITHACA, N.Y. -- Cornell University cancer researchers have revealed the molecular structure of a protein complex believed to influence the malignant transformation of cells, setting the stage for development of unique tumor-blocking drugs.
The structure of Cdc42, a molecular "switch" that turns on essential pathways in both normal and cancerous cells, and GDI (for guanine nucleotide-dissociation inhibitor), a key regulator of the Cdc42 switch, is reported in the February issue of the journal Cell (vol. 100, pp. 345-356).
"Knowing the precise, atom-by-atom structure and shape of this molecular switch (Cdc42), and the structure of other cellular proteins that regulate its activity, should eventually allow us to identify and even design small molecules that alter Cdc42 function and thereby prevent the Ras oncogene from inducing the malignant state," explains Richard A. Cerione, professor of molecular medicine in the College of Veterinary Medicine and professor of chemical biology in the College of Arts and Sciences at Cornell. The Ras oncogene is a gene that can cause cancer when it is altered.
The structure of the protein complex was mapped at MacCHESS, Cornell's high-energy synchrotron source, where the scientific technique called X-ray crystallography reveals the three-dimensional arrangement of atoms in molecules by bombarding them with intense bursts of X-rays. A "ribbon" diagram of the Cdc42/GDI complex is printed on the cover of the journal. Co-authors of the report, along with Cerione, are Gregory R. Hoffman, a Cornell graduate student in biophysics, and Nicolas Nassar, a postdoctoral associate.
The mammalian Cdc42 protein originally was purified and cloned at Cornell by researchers in Cerione's laboratory in 1990. Cdc42 is believed to play a dual role, alternating as an essential protein for normal cell growth and as a switch that allows protein from a mutated Ras oncogene to cause cancer. Many of the current strategies for int
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Contact: Roger Segelken
hrs2@cornell.edu
607-255-9736
Cornell University News Service
15-Feb-2000