Solution structure of choline binding protein A, the major adhesin of Streptococcus pneumoniae
Abstract
Streptococcus pneumoniae (pneumococcus) remains a significant health threat worldwide, especially to the young and old. While some of the biomolecules involved in pneumococcal pathogenesis are known and understood in mechanistic terms, little is known about the molecular details of bacterium/host interactions. We report here the solution structure of the 'repeated' adhesion domains (domains R1 and R2) of the principal pneumococcal adhesin, choline binding protein A (CbpA). Further, we provide insights into the mechanism by which CbpA binds its human receptor, polymeric immunoglobulin receptor (pIgR). The R domains, comprised of 12 imperfect copies of the leucine zipper heptad motif, adopt a unique 3-α-helix, raft-like structure. Each pair of α-helices is antiparallel and conserved residues in the loop between Helices 1 and 2 exhibit a novel 'tyrosine fork' structure that is involved in binding pIgR. This and other structural features that we show are conserved in most pneumococcal strains appear to generally play an important role in bacterial adhesion to pIgR. Interestingly, pneumococcus is the only bacterium known to adhere to and invade human cells by binding to pIgR.
Additional Information
© 2005 European Molecular Biology Organization. Received: 23 August 2004; accepted: 3 November 2004; published online: 16 December 2004. We acknowledge Weixing Zhang for assistance with NMR experiments, Daniel Stokes and David Cardwell for assistance with protein production, Abby Parrill for generating the homology model of CbpA-R1, Cheon-Gil Park and Ross Hilliard for help with preparation of SC-D15 and ITC experiments, Charles Ross for computer support and Charles Galea for helpful comments on the manuscript. Ranjith Muhandiram and Lewis Kay are acknowledged for graciously providing Varian NMR pulse programs. We thank Dr Eriks Kupce of Varian for recording the 900MHz 2D TROSY spectrum of CbpA-R2, and Peter M Snow and the Caltech Protein Expression Facility for expression of SC-D15. AEH was supported by the Whitehead Institute for Biomedical Research. We acknowledge support from the American Lebanese Syrian Associated Charities (ALSAC), the National Cancer Institute (CA82491 to RWK), National Center for Research Resources (RR014675 for a Biacore 3000 instrument) and a Cancer Center (CORE) Support Grant (CA 21765). We dedicate this paper to the memory of Peter M Snow who died tragically in a bicycling accident in Maine, USA, on Wednesday, August 4th.Attached Files
Supplemental Material - embj7600490-sup-0001.pdf
Supplemental Material - embj7600490-sup-0002.pdf
Supplemental Material - embj7600490-sup-0003.doc
Files
Additional details
- PMCID
- PMC544903
- Eprint ID
- 75417
- Resolver ID
- CaltechAUTHORS:20170327-122331498
- Whitehead Institute for Biomedical Research
- American Lebanese Syrian Associated Charities (ALSAC)
- NIH
- CA82491
- NIH
- RR014675
- NIH
- CA 21765
- Created
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2017-03-27Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field