title: The extracellular protein factor Epf from Streptococcus pyogenes is a cell surface adhesin that binds to cells through an N-terminal domain containing a carbohydrate-binding module.
abstract: Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment to and entry into epithelial cells is a prerequisite for a successful infection of the human host and requires adhesins. Here, we demonstrate that the multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin. An epf-deficient mutant showed significantly decreased adhesion to and internalization into human keratinocytes. Cell adhesion is mediated by the N-terminal domain of Epf (EpfN) and increased by the human plasma protein plasminogen. The crystal structure of EpfN, solved at 1.6 Å resolution, shows that it consists of two subdomains: a carbohydrate-binding module and a fibronectin type III domain. Both fold types commonly participate in ligand receptor and protein-protein interactions. EpfN is followed by 18 repeats of a domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but biophysical studies show they are predominantly α-helical and form a fiber-like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread family of adhesins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), in which a cell wall-attached stalk enables long range interactions via its adhesive N-terminal domain.
authors.affiliation: Maurice Wilkins Centre for Molecular Biodiscovery and School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Christian
authors.initials: C
authors.lastname: Linke
authors.forename: Nikolai
authors.initials: N
authors.lastname: Siemens
authors.forename: Sonja
authors.initials: S
authors.lastname: Oehmcke
authors.forename: Mazdak
authors.initials: M
authors.lastname: Radjainia
authors.forename: Ruby H P
authors.initials: RH
authors.lastname: Law
authors.forename: James C
authors.initials: JC
authors.lastname: Whisstock
authors.forename: Edward N
authors.initials: EN
authors.lastname: Baker
authors.forename: Bernd
authors.initials: B
authors.lastname: Kreikemeyer
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002241:Carbohydrates / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D008958:Models, Molecular; D009154:Mutation; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D013297:Streptococcus pyogenes / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014961:X-Ray Diffraction
chemical_list: D018829:Adhesins, Bacterial; D002241:Carbohydrates; D010958:Plasminogen