Crystal structure of a Hedgehog autoprocessing domain: homology between Hedgehog and self-splicing proteins

Cell. 1997 Oct 3;91(1):85-97. doi: 10.1016/s0092-8674(01)80011-8.


The approximately 25 kDa carboxy-terminal domain of Drosophila Hedgehog protein (Hh-C) possesses an autoprocessing activity that results in an intramolecular cleavage of full-length Hedgehog protein and covalent attachment of a cholesterol moiety to the newly generated amino-terminal fragment. We have identified a 17 kDa fragment of Hh-C (Hh-C17) active in the initiation of autoprocessing and report here its crystal structure. The Hh-C17 structure comprises two homologous subdomains that appear to have arisen from tandem duplication of a primordial gene. Residues in the Hh-C17 active site have been identified, and their role in Hedgehog autoprocessing probed by site-directed mutagenesis. Aspects of sequence, structure, and reaction mechanism are conserved between Hh-C17 and the self-splicing regions of inteins, permitting reconstruction of a plausible evolutionary history of Hh-C and the inteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Drosophila Proteins*
  • Drosophila melanogaster / chemistry
  • Drosophila melanogaster / genetics
  • Hedgehog Proteins
  • Insect Proteins / chemistry*
  • Insect Proteins / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Peptide Fragments / chemistry*
  • Protein Splicing / physiology*
  • Protein Structure, Secondary
  • Proteins / genetics
  • Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Drosophila Proteins
  • Hedgehog Proteins
  • Insect Proteins
  • Peptide Fragments
  • Proteins
  • hh protein, Drosophila

Associated data

  • PDB/1AT0
  • PDB/1AT0SF