A proposed interaction mechanism between elastin-derived peptides and the elastin/laminin receptor-binding domain

Proteins. 2009 Aug 1;76(2):461-76. doi: 10.1002/prot.22361.

Abstract

Elastin-derived peptides (EDPs) have been intensively studied in view of their widely diverse biological activities. These are triggered both in normal and tumor cells, through peptide anchoring at the surface of the elastin-binding protein (EBP), a subunit of the elastin/laminin receptor. In this study, we investigated both the structure of the Sgal peptide, representing the elastin-binding domain of EBP, and its interaction with EDPs, through a combination of experimental and theoretical methods. Although the conformation of the Sgal peptide is highly flexible, we detected a type I beta-turn at the QDEA sequence. This represents the best structured motif in the entire Sgal peptide, which might therefore contribute to its binding activity. We further propose a novel three-dimensional model for the interaction between the Sgal peptide and EDPs; folding of the EDPs at the GXXP motif, in a conformation close to a type VIII beta-turn, provides the efficient contact of the protein with the Q residue of the Sgal peptide. This residue is exposed to the peptide surface, because of the beta-turn structure of the QDEA residues in the peptide sequence. We further show that this complex is stabilized by three hydrogen bonds involving EDPs backbone atoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Circular Dichroism
  • Elastin / chemistry*
  • Elastin / metabolism
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Protein Conformation
  • Receptors, Laminin / chemistry*
  • Receptors, Laminin / metabolism*

Substances

  • Peptide Fragments
  • Receptors, Laminin
  • Elastin