Abstract
Phosphorylcholine, a specific component of the pneumococcal cell wall, is crucial in pathogenesis. It directly binds to the human platelet-activating factor (PAF) receptor and acts as a docking station for the family of surface-located choline-binding proteins (CBP). The first structure of a complete pneumococcal CBP, Pce (or CbpE), has been solved in complex with the reaction product and choline analogs. Pce has a novel modular structure, with a globular N-terminal module containing a binuclear Zn2+ catalytic center, and an elongated choline-binding module. Residues involved in substrate binding and catalysis are described and modular configuration of the active center accounts for in vivo features of teichoic acid hydrolysis. The hydrolysis of PAF by Pce and its regulatory role in phosphorylcholine decoration of the bacterial surface provide new insights into the critical function of Pce in pneumococcal adherence and invasiveness.
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Acknowledgements
The authors thank L. Serre for helpful suggestions, R. Kahn for help in data processing and analysis, Bracco Imaging (Milan) for providing a sample of Gd–HPDO3A, the staff of the BM30A beamline at the European Synchrotron Radiation Facility (Grenoble) for support and R.A. Klein for providing the atomic coordinates of the pentameric lipoteichoic acid. We thank R. López and E. García for critically reading the manuscript, W. Ran for correcting the English version and A. Torrecillas and SUIC staff for help in the ICP-OE measures. This work was supported by grants BIO2000-1307, BIO2002-02887, BIO2003-01952 and BMC2003-00074 from Dirección General de Investigación and by grant Contrato-Programa de Grupos Estratégicos (BMC2000-1002) de la Comunidad Autónoma de Madrid. L.L. and A.G. hold a fellowship from the Spanish Ministry of Science and Technology.
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Supplementary Fig. 1
Primary and secondary structures of crystallized teichoic acid phosphorylcholine esterase (Pce). (PDF 624 kb)
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Hermoso, J., Lagartera, L., González, A. et al. Insights into pneumococcal pathogenesis from the crystal structure of the modular teichoic acid phosphorylcholine esterase Pce. Nat Struct Mol Biol 12, 533–538 (2005). https://doi.org/10.1038/nsmb940
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DOI: https://doi.org/10.1038/nsmb940
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