Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex

Aberrant Hedgehog (HH) signaling leads to various types of cancer and birth defects. N-terminally palmitoylated HH initiates signaling by binding its receptor Patched-1 (PTCH1). A recent 1:1 PTCH1–HH complex structure visualized a palmitate-mediated binding site on HH, which was inconsistent with previous studies that implied a distinct, calcium-mediated binding site for PTCH1 and HH co-receptors. Here, our 3.5-Å resolution cryo-EM structure of native Sonic Hedgehog (SHH-N) in com…
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