Abstract
Phages play key roles in the pathogenicity and adaptation of the human pathogen Staphylococcus aureus. However, little is known about the molecular recognition events that mediate phage adsorption to the surface of S. aureus. The lysogenic siphophage ϕ11 infects S. aureus SA113. It was shown previously that ϕ11 requires α- or β-N-acetylglucosamine (GlcNAc) moieties on cell wall teichoic acid (WTA) for adsorption. Gp45 was identified as the receptor binding protein (RBP) involved in this process and GlcNAc residues on WTA were found to be the key component of the ϕ11 receptor. Here we report the crystal structure of the RBP of ϕ11, which assembles into a large, multidomain homotrimer. Each monomer contains a five-bladed propeller domain with a cavity that could accommodate a GlcNAc moiety. An electron microscopy reconstruction of the ϕ11 host adhesion component, the baseplate, reveals that six RBP trimers are assembled around the baseplate core. The Gp45 and baseplate structures provide insights into the overall organization and molecular recognition process of the phage ϕ11 tail. This assembly is conserved among most glycan-recognizing Siphoviridae, and the RBP orientation would allow host adhesion and infection without an activation step.
Highlights
Phages play key roles in the pathogenicity and adaptation of the human pathogen Staphylococcus aureus
Structure determination was performed with a Ta6Br12 derivative using single isomorphous replacement with anomalous scattering (SIRAS) and exploiting the non-crystallographic symmetry (NCS) present in the crystals
Our analysis defines the domain organization of receptor binding protein (RBP), which can be divided into a stem region, a platform domain and a tower-like C-terminal structure composed of two nearly identical domains
Summary
The C-terminal end of the third helical bundle abuts the three five-bladed propeller domains that form the platform of φ11 RBP (Fig. 1D). The final map has a resolution of 23 Å (determined using the 0.5 FSC criterion) and allowed us to unambiguously place six φ1 1 RBP trimers (Fig. 5A,B) To optimize this fit, we modified the hinge angle between the second and the third helix bundles from a value of ~30° to ~90°. When attaching the trimeric Tal N-terminal domain below the Dit hexamer, the three carbohydrate binding modules (2WAO) identified by HHpred project in the direction of the tail tip These three bulky modules should fill the electron density map in between the six RBP trimers
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