Modeling the Trypanosoma cruzi Tc85-11 protein and mapping the laminin-binding site

Biochem Biophys Res Commun. 2004 Dec 10;325(2):612-8. doi: 10.1016/j.bbrc.2004.10.068.

Abstract

Trypanosoma cruzi expresses a set of glycoproteins encoded by the gp85/trans-sialidase gene superfamily. In this report a structure model is proposed for a cloned member of the superfamily, the Tc85-11 protein. The structure consists of an N-terminus beta-propeller and a C-terminus beta-sandwich interconnected by an alpha-helix. The recombinant protein, corresponding to the N-domain (Tc85-N), binds to laminin in a selective manner. Six synthetic 20-mer peptides from the N-domain adhere onto the surface of LLC-MK(2) cells and two of these peptides specifically inhibit the Tc85-N/laminin interaction, indicating that they are the laminin-binding sites of the molecule. Thus, Tc85-11 and other related members of the family appear to be good candidates to play an important role in T. cruzi infection via a laminin mediated host-parasite interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Adhesion
  • Cell Line
  • Enzyme-Linked Immunosorbent Assay
  • Glycoproteins / chemistry*
  • Glycoproteins / metabolism
  • Laminin / chemistry*
  • Laminin / metabolism*
  • Macaca mulatta
  • Models, Molecular
  • Molecular Sequence Data
  • Neuraminidase / chemistry*
  • Neuraminidase / metabolism
  • Peptides / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Sialoglycoproteins / chemistry*
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / metabolism*
  • Trypanosoma cruzi / metabolism*

Substances

  • Glycoproteins
  • Laminin
  • Peptides
  • Recombinant Proteins
  • Sialoglycoproteins
  • trans-sialidase
  • Neuraminidase