Structure of KRT4 binding domain of Srr-1 from Streptococcus agalactiae reveals a novel β-sheet complementation

Int J Biol Macromol. 2015 Apr;75:97-105. doi: 10.1016/j.ijbiomac.2014.12.048. Epub 2015 Jan 17.

Abstract

The serine rich repeat protein-1 (Srr-1) is an adhesive protein of Streptococcus agalactiae. It is the first bacterial protein identified to interact with human keratin 4 (K4 or KRT4). Within Srr-1, the residues 311-641 constitute the non-repeat ligand binding region (Srr-1-BR(311-641)). The C-terminal part of Srr-1-BR(311-641), comprising of residues 485-642 (termed Srr-1-K4BD), have been identified to bind to K4. Here we report the crystal structure of recombinant Srr-1-K4BD(485-642) and its possible mode of interaction with K4 through docking studies. The dimeric structure of Srr-1-K4BD(485-642) reveals a novel two way "slide lock" parallel β-sheet complementation where the C-terminal strand of one monomer is positioned anti-parallel to the N-terminal strand of the adjacent monomer and this arrangement is not seen so far in any of the homologous structures. The dimerization of Srr-1-K4BD(485-642) observed both in the crystal structure and in solution suggests that similar domain association could also be possible in in vivo and we propose this association would likely generate a new binding site for another host molecule. It is likely that the adhesin can recognize multiple ligands using its ligand binding sub-domains through their intra and inter domain association with one another.

Keywords: Adhesin; Keratin-binding; β-sheet complementation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / chemistry*
  • Adhesins, Bacterial / metabolism*
  • Chromatography, Gel
  • Circular Dichroism
  • Crystallography, X-Ray
  • Humans
  • Keratin-4 / metabolism*
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Secondary
  • Streptococcus agalactiae / metabolism*
  • Structural Homology, Protein

Substances

  • Adhesins, Bacterial
  • Keratin-4
  • Srr-1 protein, Streptococcus agalactiae