TY - JOUR T1 - Signaling Domain of Sonic Hedgehog as Cannibalistic Calcium-Regulated Zinc-Peptidase A1 - Rebollido-Rios, Rocio A1 - Bandari, Shyam A1 - Wilms, Christoph A1 - Jakuschev, Stanislav A1 - Vortkamp, Andrea A1 - Grobe, Kay A1 - Hoffmann, Daniel Y1 - 2014/07/17 N2 - Author Summary Hedgehog proteins are important “morphogens” that steer embryonic development in concentration-dependent ways. Despite many years of intensive research, the mechanism of morphogen action is still under debate. We have studied properties of ShhN, the actual signaling part of Sonic Hedgehog, by a comprehensive set of computational methods and based on experimentally determined molecular structures. Our work suggests surprising new features of ShhN, namely that ShhN is an enzyme that acts as a cannibalistic peptidase, and that this enzymatic function is switched off by the binding of calcium ions to ShhN. Our computational approach reveals the details of this novel switching mechanism. To test the predicted autodegradation of ShhN, we study in vitro the stability of specific mutants, and we find that these experiments are in agreement with predictions. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 10 IS - 7 UR - https://doi.org/10.1371/journal.pcbi.1003707 SP - e1003707 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1003707 ER -