The PYRIN domain: a member of the death domain-fold superfamily

Protein Sci. 2001 Sep;10(9):1911-8. doi: 10.1110/ps.13801.

Abstract

PYRIN domains were identified recently as putative protein-protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The approximately 95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein-protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction.

MeSH terms

  • Amino Acid Sequence
  • Apoptosis*
  • Circular Dichroism
  • Cytoskeletal Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Folding
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / metabolism
  • Pyrin
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • Cytoskeletal Proteins
  • Proteins
  • Pyrin