The anaphylatoxin C5a is derived from the complement component C5 during
activation of the complement cascade. It is an important component in the
pathogenesis of a number of inflammatory diseases. NMR structures of human and
porcine C5a have been reported; these revealed a four-helix bundle stabilized by
three disulfide bonds. The crystal structure of human desArg-C5a has now been
determined in two crystal forms. Surprisingly, the protein crystallizes as a
dimer and each monomer in the dimer has a three-helix core instead of the
four-helix bundle noted in the NMR structure determinations. Furthermore, the
N-terminal helices of the two monomers occupy different positions relative to
the three-helix core and are completely different from the NMR structures. The
physiological significance of these structural differences is unknown.
