Sequence properties of GPI-anchored proteins near the omega-site: constraints for the polypeptide binding site of the putative transamidase

Protein Eng. 1998 Dec;11(12):1155-61. doi: 10.1093/protein/11.12.1155.


Glycosylphosphatidylinositol (GPI) anchoring is a common post-translational modification of extracellular eukaryotic proteins. Attachment of the GPI moiety to the carboxyl terminus (omega-site) of the polypeptide occurs after proteolytic cleavage of a C-terminal propeptide. In this work, the sequence pattern for GPI-modification was analyzed in terms of physical amino acid properties based on a database analysis of annotated proprotein sequences. In addition to a refinement of previously described sequence signals, we report conserved sequence properties in the regions omega - - 1 and omega + + 5. We present statistical evidence for volume-compensating residue exchanges with respect to the positions omega - + 2. Differences between protozoan and metazoan GPI-modification motifs consist mainly in variations of preferences to amino acid types at the positions near the omega-site and in the overall motif length. The variations of polypeptide substrates are exploited to suggest a model of the polypeptide binding site of the putative transamidase, the enzyme catalyzing the GPI-modification. The volume of the active site cleft accommodating the four residues omega - + 2 appears to be approximately 540 A3.

MeSH terms

  • Amino Acid Sequence
  • Aminoacyltransferases / chemistry*
  • Aminoacyltransferases / metabolism
  • Animals
  • Binding Sites
  • Conserved Sequence
  • Eukaryota
  • Glycosylphosphatidylinositols / chemistry*
  • Glycosylphosphatidylinositols / metabolism
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Peptides / metabolism*
  • Protein Binding
  • Rats
  • Sequence Analysis
  • Species Specificity
  • Yeasts


  • Glycosylphosphatidylinositols
  • Peptides
  • Aminoacyltransferases
  • transamidases

Associated data

  • SWISSPROT/P20949
  • SWISSPROT/Q60401