C5a

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C5a is a protein fragment released from complement component C5. In humans, the polypeptide contains 74 amino acids but is rapidly metabolised by a serum enzyme, carboxypeptidase B to a 73 amino acid form, C5a des-Arg. C5a is an anaphylatoxin, causing the release of histamine from mast cells; C5a des-Arg is a much less potent anaphylatoxin. However, both forms are effective leucocyte chemoattractants, causing the accumulation of white blood cells, especially neutrophil granulocytes, at sites of complement activation.

C5a binds to a receptor protein on the surface of target cells, C5aR or CD88. This is a member of the G-protein-coupled receptor superfamily of proteins, predicted to have seven transmembrane helical domains of largely hydrophobic amino acid residues, forming three intra- and three extra-cellular loops, with an extracellular N-terminus and an intracellular C-terminus. C5a binding to the receptor is a two-stage process: an interaction between basic residues in the helical core of C5a and acidic residues in the extracellular N-terminal domain allows the C-terminus of C5a to bind to residues in the receptor transmembrane domains. The latter interaction leads to receptor activation, and the transduction of the ligand binding signal across the cell plasma membrane to a cytoplasmic G protein.