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C5a is a protein fragment released from complement component C5. In humans, the polypeptide contains 74 amino acids. NMR spectroscopy proved that the molecule is composed of four helices and loops connecting the helices. On the N terminus a short 1.5 turn helix is also present.[1] The longest helix -IV- develops three disulfide bonds with helix II and III. C5a is rapidly metabolised by a serum enzyme, carboxypeptidase B to a 73 amino acid form, C5a des-Arg.
Schematic representation of three dimensional structure of complement 5a.
[edit] Functions
- C5a activates white blood cells by increasing avidity for white blood cell integrins and upregulating the Lipoxygenase pathway for arachidonic acid metabolism.
- C5a is a powerful inflammatory mediator, and seems to be a key factor in the development of pathology of many inflammatory diseases involving the complement system.
[edit] Binding process
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 the cytoplasmic G protein Gi type GNAI2[2].
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