Solution structure of the orphan PABC domain from Saccharomyces cerevisiae poly(A)-binding protein

J Biol Chem. 2002 Jun 21;277(25):22822-8. doi: 10.1074/jbc.M201230200. Epub 2002 Apr 8.


We have determined the solution structure of the PABC domain from Saccharomyces cerevisiae Pab1p and mapped its peptide-binding site. PABC domains are peptide binding domains found in poly(A)-binding proteins (PABP) and are a subset of HECT-family E3 ubiquitin ligases (also known as hyperplastic discs proteins (HYDs)). In mammals, the PABC domain of PABP functions to recruit several different translation factors to the mRNA poly(A) tail. PABC domains are highly conserved, with high specificity for peptide sequences of roughly 12 residues with conserved alanine, phenylalanine, and proline residues at positions 7, 10, and 12. Compared with human PABP, the yeast PABC domain is missing the first alpha helix, contains two extra amino acids between helices 2 and 3, and has a strongly bent C-terminal helix. These give rise to unique peptide binding specificity wherein yeast PABC binds peptides from Paip2 and RF3 but not Paip1. Mapping of the peptide-binding site reveals that the bend in the C-terminal helix disrupts binding interactions with the N terminus of peptide ligands and leads to greatly reduced binding affinity for the peptides tested. No high affinity or natural binding partners from S. cerevisiae could be identified by sequence analysis of known PABC ligands. Comparison of the three known PABC structures shows that the features responsible for peptide binding are highly conserved and responsible for the distinct but overlapping binding specificities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Conserved Sequence
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Initiation Factors / metabolism
  • Peptides / chemistry
  • Phylogeny
  • Poly(A)-Binding Proteins
  • Protein Binding
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae / metabolism*


  • Ligands
  • PAIP1 protein, human
  • Peptide Initiation Factors
  • Peptides
  • Poly(A)-Binding Proteins
  • RNA-Binding Proteins

Associated data

  • PDB/1IFW