Structural insights into proteoglycan-shaped Hedgehog signaling.

  title={Structural insights into proteoglycan-shaped Hedgehog signaling.},
  author={Daniel M. Whalen and Tomas Malinauskas and Robert J C Gilbert and Christian Siebold},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  volume={110 41},
Hedgehog (Hh) morphogens play fundamental roles during embryogenesis and adulthood, in health and disease. Multiple cell surface receptors regulate the Hh signaling pathway. Among these, the glycosaminoglycan (GAG) chains of proteoglycans shape Hh gradients and signal transduction. We have determined crystal structures of Sonic Hh complexes with two GAGs, heparin and chondroitin sulfate. The interaction determinants, confirmed by site-directed mutagenesis and binding studies, reveal a… CONTINUE READING