Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT

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Abstract
How Hedgehog gets its lipid tail: Phospholipid membranes serve as barriers between different cellular environments but are also crucial platforms for biosynthesis, signaling, and transport. In animals, the developmental signaling protein Hedgehog must be modified with an acyl group by the membrane-embedded enzyme Hedgehog acyltransferase (HHAT) to be recognized by its receptor. Using cryo–electron microscopy, Jiang et al. determined structures of HHAT bound to palmitoyl–coenzyme A or a palmitoylated peptide product. Two cavities connect at the active site, enabling acylation of Hedgehog in the lumen of the endoplasmic reticulum by lipid substrates from the cytosolic face of the membrane. Science , abg4998, this issue p. 1215
Funding Information
  • National Cancer Institute (P30 CA008748)
  • Memorial Sloan-Kettering Cancer Center (P30 CA008748)
  • Geoffrey Beene Cancer Research Center

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