3-D Structure Determined for HER3 Protein

Scientists have determined the 2.6 angstrom crystal structure of the entire extracellular region of human HER3 (ErbB3), a member of the epidermal growth factor receptor (EGFR) family. Their work was reported in the August 1, 2002, online edition of Science.

HER3 is the target of the breast cancer treatment Herceptin. The new finding may speed efforts to interfere with abnormal growth and cancer. The HER proteins are embedded in the cell membrane. Each molecule consists of three parts: a region outside the cell that recognizes and binds certain molecules; a region that anchors the protein in the cell membrane; and a region inside the cell that, when activated, adds phosphates to various proteins.

The researchers, from Johns Hopkins University (Baltimore, MD, USA), employed several methods to purify large amounts of the HER3 receptor region, and used this material to prepare uniform crystals, crucial for deciphering protein structures. By bombarding the crystals with x-rays at the National Synchrotron Light Source at Brookhaven National Laboratory in New York (NY, USA), they obtained sufficient data to generate a 3-D model.

"It took us more than two years to interpret the data and get HER3's structure,” explained Dr. Dan Leahy, professor of biophysics in Johns Hopkins' Institute for Basic Biomedical Sciences. "Now that we have it, it might take only weeks to figure out its relatives. Finding out the shapes of the entire HER family of proteins, HER1, HER2 and HER4, will provide the first opportunity to rationally design new drugs to interfere with them, possibly preventing or treating select forms of cancer.”