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Nearly a century after the significance of the human complement system was recognized, we have come to realize that its functions extend far beyond the elimination of microbes. Complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris(More)
Factor H (FH) is an abundant regulator of complement activation and protects host cells from self-attack by complement. Here we provide insight into the regulatory activity of FH by solving the crystal structure of the first four domains of FH in complex with its target, complement fragment C3b. FH interacted with multiple domains of C3b, covering a large,(More)
The human immune system has developed an elaborate network of cascades for dealing with microbial intruders. Owing to its ability to rapidly recognize and eliminate microorganisms, the complement system is an essential and efficient component of this machinery. However, many pathogenic organisms have found ways to escape the attack of complement through a(More)
The complement system is a central component of innate immunity and bridges the innate to the adaptive immune response. However, it can also turn its destructive capabilities against host cells and is involved in numerous diseases and pathological conditions. Modulation of the complement system has been recognized as a promising strategy in drug discovery,(More)
As a key part of the innate immune system, complement plays an important role not only in defending against invading pathogens but also in many other biological processes. Inappropriate or excessive activation of complement has been linked to many autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. A(More)
Activation of the complement system generates potent chemoattractants and leads to the opsonization of cells for immune clearance. Short-lived protease complexes cleave complement component C3 into anaphylatoxin C3a and opsonin C3b. Here we report the crystal structure of the C3 convertase formed by C3b and the protease fragment Bb, which was stabilized by(More)
Staphylococcus aureus possesses an impressive arsenal of complement evasion proteins that help the bacterium escape attack of the immune system. The staphylococcal complement inhibitor (SCIN) protein exhibits a particularly high potency and was previously shown to block complement by acting at the level of the C3 convertases. However, many details about the(More)
Therapeutic modulation of the human complement system is considered a promising approach for treating a number of pathological conditions. Owing to its central position in the cascade, component C3 is a particularly attractive target for complement-specific drugs. Compstatin, a cyclic tridecapeptide, which was originally discovered from phage-display(More)
Chronic periodontitis is induced by a dysbiotic microbiota and leads to inflammatory destruction of tooth-supporting connective tissue and bone. The third component of complement, C3, is a point of convergence of distinct complement activation mechanisms, but its involvement in periodontitis was not previously addressed. We investigated this question using(More)
When excessively activated or deregulated, complement becomes a major link between infection and inflammatory pathology including periodontitis. This oral inflammatory disease is associated with a dysbiotic microbiota, leads to the destruction of bone and other tooth-supporting structures, and exerts an adverse impact on systemic health. We have previously(More)