The Structure of SHH in Complex with HHIP Reveals a Recognition Role for the Shh Pseudo Active Site in Signaling

Bosanac, I., et al., 16(7), 691-697, Nature Structural & Molecular Biology, 2009

Hedgehog (Hh) signaling is crucial for many aspects of embryonic development, whereas dysregulation of this pathway is associated with several types of cancer. In this publication, the binding interactions of various proteins involved in the Hh signaling pathway are studied and the mechanism of binding revealed through X-ray crystal structures and Octet platform binding assays. Binding kinetics of hedgehog-interacting protein (HHIP) fragments and HHIP mutants to Sonic hedgehog (SHH) were studied using the Octet system. Streptavidin biosensors were loaded with biotinylated-SHHN-Cys and transferred to wells containing HHIP proteins at concentrations of 1.2, 1.0, 0.8 and 0.6 μM in kinetic buffer. Kinetic parameters (kon and koff) and affinities (KD) were reported.

Read More