Structural Biology

Interfering with Receptors

Science's STKE  27 Aug 2002:
Vol. 2002, Issue 147, pp. tw316-TW316
DOI: 10.1126/stke.2002.147.tw316

The family of receptors for epidermal growth factor (EGF) transmits signals critical for growth and differentiation of cells in a wide variety of tissues during development. Inappropriate expression of these receptors occurs in many human cancers, and Herceptin, an antibody against one of these receptors (HER2), is used in the treatment of breast cancer. Cho and Leahy present the 2.6 angstrom crystal structure of the entire extracellular portion of one member of this receptor family, HER3. One of the L-shaped halves sits atop the other and assumes a toroidal shape with a protruding spur. Previously mapped regions of the EGF binding site, on the spur and the torus, must be brought together in order to interact productively with the ligand. Interference with this large-scale conformational change might offer a promising route to therapeutics.

H.-S. Cho, D. J. Leahy, Structure of the extracellular region of HER3 reveals an interdomain tether, Science 297, 1330-1333 (2002). [Abstract] [Full Text]