The hedgehog multigene family encodes cell-cell signaling molecules critical in embryonic development. Foundational knowledge about development and cell-cell communication will assist in our understanding of diseases such as cancer where growth and signaling are aberrant and may also lead to new therapies for other diseases by allowing regeneration of lost tissues.
The specific aims of this project are (1) Determination of the crystal structure of the hedgehog C-terminal domain, (2) Determination of the crystal structure of the hedgehog full-length protein, and (3) Analysis of the general structural features of hedgehog protein and the implications of these structures for the function of hedgehog in development. Diffraction-quality crystals of the C-terminal domain of hedgehog have been grown. The crystals diffract to 2.3A resolution. A K2PtC14 derivative data set was also collected. Additional heavy atom derivatives of the C-terminal domain will be prepared, including a selenomethionine- substituted derivative that can be used to solve the crystallographic phase problem by the multiwavelength anomalous diffraction method. The structure of the full-length protein will be solved by molecular replacement using the previously solved N-and C-terminal domain structures.
