A "dock, lock, and latch" structural model for a staphylococcal adhesin binding to fibrinogen

Cell. 2003 Oct 17;115(2):217-28. doi: 10.1016/s0092-8674(03)00809-2.

Abstract

Gram-positive pathogens such as staphylococci contain multiple cell wall-anchored proteins that serve as an interface between the microbe and its environment. Some of these proteins act as adhesins and mediate bacterial attachment to host tissues. SdrG is a cell wall-anchored adhesin from Staphylococcus epidermidis that binds to the Bbeta chain of human fibrinogen (Fg) and is necessary and sufficient for bacterial attachment to Fg-coated biomaterials. Here, we present the crystal structures of the ligand binding region of SdrG as an apoprotein and in complex with a synthetic peptide analogous to its binding site in Fg. Analysis of the crystal structures, along with mutational studies of both the protein and of the peptide, reveals that SdrG binds to its ligand with a dynamic "dock, lock, and latch" mechanism. We propose that this mechanism represents a general mode of ligand binding for structurally related cell wall-anchored proteins of gram-positive bacteria.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adhesins, Bacterial / chemistry*
  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / metabolism*
  • Alanine / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Bacterial Adhesion
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Conserved Sequence
  • Crystallography, X-Ray
  • Fibrinogen / chemistry
  • Fibrinogen / drug effects
  • Fibrinogen / metabolism*
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Peptides / chemistry
  • Peptides / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • Serine / metabolism
  • Staphylococcus epidermidis / metabolism*
  • Thrombin / pharmacology

Substances

  • Adhesins, Bacterial
  • Bacterial Proteins
  • Ligands
  • Peptides
  • Serine
  • Fibrinogen
  • Thrombin
  • Alanine

Associated data

  • PDB/1R17
  • PDB/1R19