Date Published: July 1, 2011
Publisher: International Union of Crystallography
Author(s): Pietro Roversi, Steven Johnson, Joseph J. E. Caesar, Florence McLean, Kirstin J. Leath, Stefanos A. Tsiftsoglou, B. Paul Morgan, Claire L. Harris, Robert B. Sim, Susan M. Lea.
The structure of rat CrrY1–4 determined in two distinct crystal forms shows a pronounced bend at the interface between domains 3 and 4.
Complement constitutes the most ancient arm of the immune system, providing a first line of defence against blood infection by pathogens, and links innate to cellular immunity (Ricklin et al., 2010 ▶). Prevention of activation on self-surfaces is achieved by complement regulatory proteins (Liszewski et al., 1996 ▶). The two main complement regulation mechanisms that protect self-tissue from unwanted complement activation are decay-acceleration activity (DAA), in which the regulator dissociates the complement-activating C3 and C4 convertases, and factor I cofactor activity (CA), in which the regulator assists the serine protease factor I in cleaving and degrading the same C3 and C4 convertase precursors, C4b and C3b (Walport, 2001a ▶,b ▶).
The two crystal structures of rat CrrY1–4 show a hockey-stick-shaped molecule with the elongated handle comprising CCP domains 1–3, with approximate dimensions 25 × 25 × 120 Å, and the blade made by CCP domain 4 (Fig. 1 ▶a). The electron density of the crystal form diffracting to 2.5 Å resolution allowed unambiguous tracing of residues 37–290 (Fig. 1 ▶b). The loop 52–54 is poorly ordered in the lower resolution structure. The domains are standard CCP domains and are organized in β-sheets held together by two disulfide bridges (Fig. 2 ▶a).