Download MendeleyThree-Dimensional Structure and Biophysical Characterization of Staphylococcus aureus Cell Surface Antigen-Manganese Transporter MntC.
Gribenko, A., Mosyak, L., Ghosh, S., Parris, K., Svenson, K., Moran, J., Chu, L., Li, S., Liu, T., Woods, V.L., Jansen, K.U., Green, B.A., Anderson, A.S., Matsuka, Y.V.(2013) J Mol Biol 425: 3429-3445
- PubMed: 23827136
- DOI: https://doi.org/10.1016/j.jmb.2013.06.033
- Primary Citation of Related Structures:
4K3V - PubMed Abstract:
MntC is a metal-binding protein component of the Mn²⁺-specific mntABC transporter from the pathogen Staphylococcus aureus. The protein is expressed during the early stages of infection and was proven to be effective at reducing both S. aureus and Staphylococcus epidermidis infections in a murine animal model when used as a vaccine antigen. MntC is currently being tested in human clinical trials as a component of a multiantigen vaccine for the prevention of S. aureus infections. To better understand the biological function of MntC, we are providing structural and biophysical characterization of the protein in this work. The three-dimensional structure of the protein was solved by X-ray crystallography at 2.2Å resolution and suggests two potential metal binding modes, which may lead to reversible as well as irreversible metal binding. Precise Mn²⁺-binding affinity of the protein was determined from the isothermal titration calorimetry experiments using a competition approach. Differential scanning calorimetry experiments confirmed that divalent metals can indeed bind to MntC reversibly as well as irreversibly. Finally, Mn²⁺-induced structural and dynamics changes have been characterized using spectroscopic methods and deuterium-hydrogen exchange mass spectroscopy. Results of the experiments show that these changes are minimal and are largely restricted to the structural elements involved in metal coordination. Therefore, it is unlikely that antibody binding to this antigen will be affected by the occupancy of the metal-binding site by Mn²⁺.
Organizational Affiliation:
Pfizer Vaccine Research, 401 North Middletown Road, Pearl River, NY 10965, USA. Alexey.Gribenko@pfizer.com
