Mark J. van Raaij
Centro Nacional de Biotecnologia - CSIC
Department of Macromolecular Structure
Mark van Raaij is a tenured scientist of the Spanish National Research Council, working at the National Biotechnology Centre in Madrid. He is a structural biologist and crystallographer trained at the MRC LMB in Cambridge and EMBL in Grenoble. His group Structural Biology of Virus Proteins in the Department of Macromolecular Structure is interested in high-resolution structures of phage receptor-binding proteins and lysins, where possible in complex with their bacterial receptors and substrates. Mark is a member of the ISVM Scientific Advisory Board and Main Editor of the International Union of Crystallography journal Acta Crystallographica F.
Affiliations: (1). Centro Nacional de Biotecnologia - CSIC, calle Darwin (3), (28049) Madrid (Spain)
Most bacteriophages recognize their host cells via specialized spike or fibre proteins. The overall goal of our group is to determine their structures in complex with their natural receptors. We also study the high-resolution structures of endolysin proteins, involved in bacterial wall degradation. Bacteriophage epsilon15 infects Salmonella enterica subspecies enterica, serovar Anatum A1. This bacterium has a lipo-polysaccharide O-antigen consisting of units of D-O-acetyl-galactose-alpha1-6-D-mannose-beta1-4-L-rhamnose. Lysogenic epsilon15 blocks acetylation of the O-antigen and favours production of beta-linked O-antigen. The receptor-binding fibre protein is gp20. Gp20 consists of an N-terminal triple coiled-coiled virus binding domain (not resolved in our structures), a central beta-helix domain with O-antigen hydrolysis activity, a lectin domain and a C-terminal esterase domain. The O-antigen hydrolysis and esterase activities were proven by mutational analysis and NMR spectroscopy. The O-antigen hydrolysis proceeds through an inversion mechanism. The importance of the esterase activity for infection is unknown. The RBP of bacteriophage S24-1 has been identified as orf16, a 642 amino acid protein. We have solved the structure and shown it is very similar to the RBP of Staphylococcus phages phi11 and P68. Teichoic acid may be a receptor for the protein, and we were able to co-crystallize the protein with a teichoic acid analogue. Pseudomonas phage JG004 endolysin Pae87 is a monomodular lysozyme. We solved its structure without and with a peptidoglycan fragment NAG-MurNAc-LAla-DGlu, suggesting that a region of the muramidase domain functions as a de facto cell wall binding domain.