Max-Planck-Institut für Kolloid- und Grenzflächenforschung
Interaction of phage Tail-Spike Proteins with O-antigenic polysaccharides
Tailspike protein (TSP) of the bacteriophage Sf6 binding to O-antigen polysaccharides on the outer membrane of the bacterial cell. (a) Structure of a lipopolysaccharide (LPS) on the outer membrane. A fragment of the O-antigen is shown, where each repeat unit (RU) has a length of around 1.4 nm. (b) Structure of the TSP with a tetrasaccharide (α-l-Rhap-(1-3)-β-d-GlcpNAc-(1-2)-α-l-Rhap-(1-2)- α-l-Rhap, corresponding to 1 RU) bound to the inter-subunit groove of the protein (inside the red ellipse). (c) A close-up view of the bound tetrasaccharide together with several important residues (ball-and-stick model) of the protein. (d) Schematic view of a bacteriophage Sf6 attached to a bacterial cell.
Tailspike protein (TSP) of the bacteriophage Sf6 binding to O-antigen polysaccharides on the outer membrane of the bacterial cell. (a) Structure of a lipopolysaccharide (LPS) on the outer membrane. A fragment of the O-antigen is shown, where each repeat unit (RU) has a length of around 1.4 nm. (b) Structure of the TSP with a tetrasaccharide (α-l-Rhap-(1-3)-β-d-GlcpNAc-(1-2)-α-l-Rhap-(1-2)- α-l-Rhap, corresponding to 1 RU) bound to the inter-subunit groove of the protein (inside the red ellipse). (c) A close-up view of the bound tetrasaccharide together with several important residues (ball-and-stick model) of the protein. (d) Schematic view of a bacteriophage Sf6 attached to a bacterial cell.
The Tailspike-Protein of bacteriophage Sf6 Bacteriophages can penetrate the dense coating of bacterial cells that are covered with Lipo-Polysaccharides (LPS), and subsequently inject their DNA without destroying the cell. The first steps of infection comprise the recognition of the long O-antigenic polysaccharides of the LPS by the tail spike proteins (TSP) of the phages and successive cleavage. Characterizing the binding mode of TSP-LPS is challenging for experiment. Here, we investigate atomistic models of the binding of small O-antigen fragments across various sites of the TSP by several state-of-the-art molecular dynamics based approaches. Why does, for instance, cleavage occur continually, making an Octasaccharide repeat unit the most abundant product observerd in hydrolysis? (see figure).
A concise picture of the bacterial LPS recognition by TSP of bacteriophages is important in order to understand the essential steps of phage infection, and to further develop phage therapy against bacterial infectious diseases.
This project is conducted in close collaboration with Dr. Steffi Barbirz, Institute of Physical Biochemistry at the University of Potsdam.
