Cellular and Molecular Bioengineering

, Volume 5, Issue 1, pp 32–43 | Cite as

Complement Inhibition by Staphylococcus aureus: Electrostatics of C3d–EfbC and C3d–Ehp Association

  • Ronald D. GorhamJr.
  • Chris A. Kieslich
  • Dimitrios MorikisEmail author


Virulence factors EfbC and Ehp from Staphylococcus aureus are potent inhibitors of complement activation. Both are excessively charged and bind to complement protein C3d at an acidic interface. We computationally generated single-alanine mutants of charged residues in the C3d–EfbC and C3d–Ehp complexes, and utilized electrostatic clustering and Poisson–Boltzmann free energy calculations to evaluate the role of electrostatics in association. Our results indicate that both interfacial electrostatic interactions and electrostatic potential distribution are crucial for C3d–EfbC and C3d–Ehp association. The results presented herein serve as a predictive tool in the selection of mutants with desired binding and immunological activity, and will narrow the search for viable candidates for further computational and experimental analyses. This study serves as the foundation for development of an inhibitor of the C3d–EfbC and C3d–Ehp interactions to combat bacterial infection and design of a complement inhibitor using EfbC and Ehp as a model.


C3 Bacterial infection Poisson–Boltzmann electrostatics Electrostatic clustering Electrostatic free energy Alanine scan 



Complement component 3


Inactivated C3b


d-fragment or thioester domain of C3


Complement receptor 2


Extracellular fibrinogen-binding protein


Efb-homologous protein


C-terminal fragment of Efb


Localized difference


Macroglobulin domain 1


Complement control protein

Supplementary material

12195_2011_195_MOESM1_ESM.pdf (1.9 mb)
Supplementary material 1 (PDF 1939 kb)


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Copyright information

© Biomedical Engineering Society 2011

Authors and Affiliations

  • Ronald D. GorhamJr.
    • 1
  • Chris A. Kieslich
    • 1
  • Dimitrios Morikis
    • 1
    Email author
  1. 1.Department of BioengineeringUniversity of California at RiversideRiversideUSA

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