CaltechAUTHORS
  A Caltech Library Service

Solution structure of choline binding protein A, the major adhesin of Streptococcus pneumoniae

Luo, Rensheng and Mann, Beth and Lewis, William S. and Rowe, Arthur and Heath, Richard and Stewart, Michael L. and Hamburger, Agnes E. and Sivakolundu, Siva and Lacy, Eilyn R. and Bjorkman, Pamela J. and Tuomanen, Elaine and Kriwacki, Richard W. (2005) Solution structure of choline binding protein A, the major adhesin of Streptococcus pneumoniae. EMBO Journal, 24 (1). pp. 34-43. ISSN 0261-4189. PMCID PMC544903. https://resolver.caltech.edu/CaltechAUTHORS:20170327-122331498

[img] PDF (Suppl. Figure 1) - Supplemental Material
See Usage Policy.

809Kb
[img] PDF (Suppl. Figure 2) - Supplemental Material
See Usage Policy.

696Kb
[img] MS Word (Suppl. Doc) - Supplemental Material
See Usage Policy.

99Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20170327-122331498

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/sj.emboj.7600490DOIArticle
http://onlinelibrary.wiley.com/doi/10.1038/sj.emboj.7600490/abstractPublisherArticle
http://onlinelibrary.wiley.com/wol1/doi/10.1038/sj.emboj.7600490/suppinfoPublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC544903/PubMed CentralArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
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.
Funders:
Funding AgencyGrant Number
Whitehead Institute for Biomedical ResearchUNSPECIFIED
American Lebanese Syrian Associated Charities (ALSAC)UNSPECIFIED
NIHCA82491
NIHRR014675
NIHCA 21765
Subject Keywords:bacterial pathogenesis; calorimetry; protein–protein interactions; solution NMR; surface plasmon resonance
Issue or Number:1
PubMed Central ID:PMC544903
Record Number:CaltechAUTHORS:20170327-122331498
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170327-122331498
Official Citation:Luo, R., Mann, B., Lewis, W. S., Rowe, A., Heath, R., Stewart, M. L., Hamburger, A. E., Sivakolundu, S., Lacy, E. R., Bjorkman, P. J., Tuomanen, E. and Kriwacki, R. W. (2005), Solution structure of choline binding protein A, the major adhesin of Streptococcus pneumoniae. The EMBO Journal, 24: 34–43. doi: 10.1038/sj.emboj.7600490
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75417
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:27 Mar 2017 21:04
Last Modified:30 Sep 2020 18:28

Repository Staff Only: item control page