"This was a puzzle, because the antibody response is specific and limited to a single M protein type, while C4BP binds a broad variety of M protein types, perhaps up to 90 percent of them," said Ghosh.
To determine if this was possible, a graduate student in Ghosh's lab, Cosmo Buffalo, collaborated with another graduate student, Sophia Hirakis, in the laboratory of Rommie Amaro, a professor of chemistry and biochemistry who uses computers to study protein structures, to first study the complex interactions between M protein and C4BP.
In their experimental and computational study, the biochemists painstakingly detailed four crystal structures of four different M protein types, each bound to human C4BP.
"These common patterns are what is used to recruit C4BP to the surface of group A Strep by the different M protein types."
The normal levels of plasma C1q, properdin, Bb, C4BP, factor H, and C3 were 61.96 [+ or -] 10.50 [micro]g/mL, 22.58 [+ or -] 9.67 [micro]g/mL, 0.69 [+ or -] 0.45 [micro]g/mL, 326.59 [+ or -] 87.25 [micro]g/mL, 515.04 [+ or -] 134.08 [micro]g/mL, and 0.80 [+ or -] 0.17mg/mL, respectively.
C4BP is the main fluid-phase inhibitor of the complement activation.
There was no significant difference in C4BP levels between patients with scanty immune deposits and immune complex deposits lupus nephritis (P = 0.389).
Escherichia coli, a cause for neonatal meningitis, crosses the blood-brain barrier by surviving in the serum where it binds to C4BP .
Complement regulators factor H, FHL-1, and C4BP have also been localised in amyloid plaques and fH and C4BP have been shown to bind A[beta] in vitro [276-278].
There is an increase in serum levels of classical pathway complement proteins such as C1q, C1, C3, and C4; increased total complement activity ([CH.sub.50]), CR1 levels; and decreased C4BP levels [307-309].
Pietrocola et al., "Capturing host-pathogen interactions by protein microarrays: identification of novel streptococcal proteins binding to human fibronectin, fibrinogen, and C4BP
," FASEB Journal, vol.
Soluble complement regulators, such as C1-inhibitor, anaphylatoxins inhibitor, C4b binding protein (C4BP
), complement factor H (CFH), complement factor I (CFI), clusterin, and vitronectin, restrict the action of complement in human tissues at multiple sites of the cascade reaction (see Figure 1).