much more easily in the presence of sialic acid, which is a component of most cells in the human body; conversely, in the absence of sialic acid, factor B can bind C3b more easily. This means that if C3b is bound to a "self" cell, the presence of sialic acid and the binding of factor H will prevent the complement cascade from activating; if C3b is bound to a bacterium, factor B will bind and the cascade will be set off as normal. This mechanism of immune regulation using Factor H has been exploited by several bacterial pathogens. Structure RCA proteins typically possess CCP domains, also termed Sushi domains or Short Consensus Repeats (SCR). Such beta-sandwich domains contain about 60 amino acid residues, each with 4 conserved cysteines arranged in two conserved disulfide bonds (oxidized in 'abab' manner), and a conserved tryptophan, but otherwise can vary greatly in sequence. Recently, it has been demonstrated that the order, spatial relationship, and structure of these domains is essential for determining function. The first CCP structure determined was a solution structure of the 16th module of factor H (pdb:1hcc). Since then, other CCP domains have been solved either by NMR-spectroscopy (also relaxation studies, e.g. module 2 and 3 from CD55 (pdb:1nwv)) or by X-ray diffraction (also with co-crystallized partner, e.g. CR2 CCP modules complexed with C3d (pdb:1ghq)). Clinical significance Complement has been implicated in many diseases associated with inflammation and autoimmunity. Efforts to develop therapeutics that target the interactions between the RCA network, CCPs, and components of the complement system have led to the development of successful drugs including Eculizumab. There are two primary mechanisms by which dysfunction of complement can contribute to tissue damage: Decreased protection of host tissues from complement activation due to the absence or lack of function of CCPs Exhaustion of CRAs due to exposure of host cells that activate complement (either through direct damage or dysfunction) or prolonged attack by a potential pathogen such as during sepsis The importance of complement regulation for good health is highlighted by recent work that seems to imply that individuals carrying point mutations or single nucleotide polymorphisms in their genes for factor H may be more susceptible to diseases including atypical hemolytic uremic syndrome, dense deposit diseases (or membranoproliferative glomrulonephritis type 2) and - most notably because of its prevalence in the elderly - age-related macular degeneration. Transgenic pigs that express human