A 'Collagen Hug' model for Staphylococcus aureus CNA binding to collagen

EMBO J. 2005 Dec 21;24(24):4224-36. doi: 10.1038/sj.emboj.7600888. Epub 2005 Dec 15.

Abstract

The structural basis for the association of eukaryotic and prokaryotic protein receptors and their triple-helical collagen ligand remains poorly understood. Here, we present the crystal structures of a high affinity subsegment of the Staphylococcus aureus collagen-binding CNA as an apo-protein and in complex with a synthetic collagen-like triple helical peptide. The apo-protein structure is composed of two subdomains (N1 and N2), each adopting a variant IgG-fold, and a long linker that connects N1 and N2. The structure is stabilized by hydrophobic inter-domain interactions and by the N2 C-terminal extension that complements a beta-sheet on N1. In the ligand complex, the collagen-like peptide penetrates through a spherical hole formed by the two subdomains and the N1-N2 linker. Based on these two structures we propose a dynamic, multistep binding model, called the 'Collagen Hug' that is uniquely designed to allow multidomain collagen binding proteins to bind their extended rope-like ligand.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adhesins, Bacterial / chemistry*
  • Adhesins, Bacterial / metabolism
  • Collagen / chemistry*
  • Crystallography, X-Ray
  • DNA / chemistry
  • Dose-Response Relationship, Drug
  • Extracellular Matrix / chemistry
  • Immunoglobulin G / chemistry
  • Ligands
  • Models, Biological
  • Models, Molecular
  • Peptides / chemistry
  • Polymerase Chain Reaction
  • Protein Binding
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Staphylococcus aureus / metabolism*
  • Surface Plasmon Resonance

Substances

  • Adhesins, Bacterial
  • Immunoglobulin G
  • Ligands
  • Peptides
  • adhesin, Staphylococcus aureus
  • Collagen
  • DNA