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Structure of the bacterial teichoic acid polymerase TagF provides insights into membrane association and catalysis

Nature Structural & Molecular Biology volume 17, pages 582–589 (2010)Cite this article

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Abstract

Teichoic acid polymers are composed of polyol-phosphate units and form a major component of Gram-positive bacterial cell walls. These anionic compounds perform a multitude of important roles in bacteria and are synthesized by monotopic membrane proteins of the TagF polymerase family. We have determined the structure of Staphylococcus epidermidis TagF to 2.7-Å resolution from a construct that includes both the membrane-targeting region and the glycerol-phosphate polymerase domains. TagF possesses a helical region for interaction with the lipid bilayer, placing the active site at a suitable distance for access to the membrane-bound substrate. Characterization of active-site residue variants and analysis of a CDP-glycerol substrate complex suggest a mechanism for polymer synthesis. With the importance of teichoic acid in Gram-positive physiology, this elucidation of the molecular details of TagF function provides a critical new target in the development of novel anti-infectives.

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Figure 1: Teichoic acid chemical structure and nature of TagF polymerization reaction.
Figure 2: Structural features of S. epidermidis TagF membrane-binding and catalytic domains.
Figure 3: Oligomeric assembly of TagF.
Figure 4: Environment of conserved TagF-family histidine residues.
Figure 5: Interaction of TagF with the CDP-glycerol substrate.

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Acknowledgements

We thank G. Olovsson for maintenance of X-ray facilities. This work was made possible by operating grants from the Canadian Institutes of Health Research and Howard Hughes Medical Institute and infrastructure grants from the Michael Smith Foundation of Health Research and the Canadian Foundation of Innovation (to N.C.J.S.). N.C.J.S. is a Howard Hughes Medical Institute international research scholar and Michael Smith Foundation for Health Research Senior Scholar. E.D.B. was supported by a salary award from the Canada Research Chairs program and operating funds from the Canadian Institutes of Health Research (MOP-15496). We are grateful for beam time and assistance at the Advanced Light Source and Canadian Light Source.

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  1. Andrew L Lovering

    Present address: Present address: School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK.,

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Vancouver, Canada

    Andrew L Lovering, Leo Y-C Lin, Thomas Spreter & Natalie C J Strynadka

  2. Center for Blood Research, University of British Columbia, Vancouver, Canada

    Andrew L Lovering, Leo Y-C Lin, Thomas Spreter & Natalie C J Strynadka

  3. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada

    Edward W Sewell & Eric D Brown

  4. Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada

    Edward W Sewell & Eric D Brown

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Contributions

A.L.L. was responsible for the cloning, purification, crystallization and all X-ray and structural analyses; E.W.S. performed and analyzed kinetic assays; L.Y.-C.L. designed and tested the heparin purification procedure; T.S. contributed to crystallographic data processing and manuscript preparation; A.L.L., E.D.B. and N.C.J.S. were responsible for experimental design and manuscript preparation.

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Correspondence to Natalie C J Strynadka.

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Lovering, A., Lin, LC., Sewell, E. et al. Structure of the bacterial teichoic acid polymerase TagF provides insights into membrane association and catalysis. Nat Struct Mol Biol 17, 582–589 (2010). https://doi.org/10.1038/nsmb.1819

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