| Abstract | Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defence [ 1431125]. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments [2777798]. 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 [2777798, 3081348]: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability [3081348]. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals [3081348]. The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulphide bridges [3081348].
Fibulins are secreted
glycoproteins that become incorporated into a fibrillar extracellular matrix when
expressed by cultured cells or added exogenously to cell monolayers [2269669, 12778127]. 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 alpha-helical fold that is stabilized 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 [8245130]. The ProDom signature in this entry does not hit the fibulins. |
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