Undergraduate Research Journal

Molecular Analysis of the Interaction Between Staphylococcus aureus Protein Sbi and Immune System Protein C3d
Wilson Rodriguez
Table 1. C3d-Sbi intermolecular
Coulombic interactions for complex 1.
Using 6Å Oxygen-Nitrogen cut-off. 11
Table 2. C3d-Sbi intermolecular Coulombic
interactions for complex 2. Using 6Å Oxygen-
Nitrogen cut-off. 11
Figure 4. Molecular graphics representations of C3d-Sbi located at two separate binding sites: complex 1 and 2. (A) Complex 1
binding interface of C3d-Sbi. Sbi (green) shown binding to concave side of C3d (cyan). C3d-Sbi backbones depicted as ribbons. (B)
Complex 2 binding interface of C3d-Sbi. Sbi (purple) shown binding to convex side of C3d (cyan). C3d-Sbi backbones depicted as
ribbons. Acidic (red) and Basic (blue) interacting residues shown on both C3d and Sbi on both complex sites in stick representation.
Residues shown in stick representations are within 6Å and depict the pairs of Tables 1 and 2.
the mutants according to electrostatic similarities. From
our results it is notable that Sbi shares several binding
similarities at Complex 1 with Efb-C and Ehp, two
proteins also secreted by S. aureus. 9 Efb-C and Ehp
interact with C3d or the C3d domain of C3/C3b to
disarm complement system function against bacteria.
Looking at the free energies (Fig. 3) and Coulombic
interactions (Table 1) we note that three mutations on
Sbi, Lys53, Arg45 and Arg20, are unfavorable to the
stability of the complex, and are therefore assumed
to be critical residues for binding. Because of the
similarities Sbi shares with Efb-C and Ehp, there could
be a possibility to develop novel therapeutics for Sbi
targeting the binding site of Complex 1, which could
also function against Efb-C and Ehp binding. Although
at Complex 2 we did not see typical clustering of an
interaction that relies primarily on electrostatics while it
may be probable that Sbi’s function at that binding site is
to block the thioester-forming residues from anchoring
C3b to antigen surfaces. The range of free energies of
association is small and a single mutation of Asp 22 to
alanine produced a completely unfavorable interaction
with positive free energies (Fig. 3b). Another possibility
is that the interaction found at Complex site 2 may be
a crystallographic artifact or may be non-electrostatic
in nature.
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