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

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.