title: 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.
authors.affiliation: Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India.
authors.forename: Ramya
authors.initials: R
authors.lastname: Sundaresan
authors.affiliation: Institute of Microbiology and Biotechnology, University of Ulm, Albert-Einstein-Allee 11 89081, Ulm, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Samen
authors.affiliation: Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India. Electronic address: pkarthe@hotmail.com.
authors.forename: Karthe
authors.initials: K
authors.lastname: Ponnuraj
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D002850:Chromatography, Gel; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006801:Humans; D053527:Keratin-4 / Q000378:metabolism*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D013292:Streptococcus agalactiae / Q000378:metabolism*; D040681:Structural Homology, Protein
chemical_list: D018829:Adhesins, Bacterial; D053527:Keratin-4; C524542:Srr-1 protein, Streptococcus agalactiae
keywords: Adhesin; Keratin-binding; β-sheet complementation