This entry represents complement component C4-A. C4-A is proteolytically processed to generate subcomponents C4a and C4b by complement component activated C1s (classical pathway) []or mannan-binding lectin-associated serine peptidases (lectin pathway) [, ]. C4a is an anaphylatoxin, whereas C4b forms a complex with complement subcomponent C2a to form the C3/C5 convertase, which is stabilized by Mg2+[, ]. The C3/C5 convertase has trypsin-like specificity [].
Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defence []. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments []. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins [, ]: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability []. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals []. The proteins are highly hydrophilic, with a mainly α-helical structure held together by 3 disulphide bridges [].
This entry represents C3a, C4a and C5a anaphylatoxins, which are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to a three-fold repeat in fibulins.Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defence []. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments []. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins [, ]: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability []. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals []. The proteins are highly hydrophilic, with a mainly α-helical structure held together by 3 disulphide bridges [].Fibulins are secreted glycoproteins that become incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers [, ]. The five known members of the family share an elongated structure and many calcium-binding sites, owing to the presence of tandem arrays of epidermal growth factor-like domains. They have overlapping binding sites for several basement-membrane proteins, tropoelastin, fibrillin, fibronectin and proteoglycans, and they participate in diverse supramolecular structures. The amino-terminal domain I of fibulin consists of three anaphylatoxin-like (AT) modules, each approximately 40 residues long and containing four or six cysteines. The structure of an AT module was determined for the complement-derived anaphylatoxin C3a, and was found to be a compact α-helical fold that is stabilised by three disulphide bridges in the pattern Cys1-4, Cys2-5 and Cys3-6 (where Cys is cysteine). The bulk of the remaining portion of the fibulin molecule is a series of nine EGF-like repeats [].
Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defence []. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments []. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins [, ]: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability []; they also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals []. The proteins are highly hydrophilic, with a mainly α-helical structure held together by 3 disulphide bridges [].Some of the proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Complement C4 belongs to the Chido/Rodgers blood group system and is associated with Ch1 to Ch6, WH, Rg1 and Rg2 antigens.
