Structural and functional characterization of complement c8γ, a member of the lipocalin protein family

Abstract

Human complement component C8 exhibits an unusual structure in that it contains three chains, two of which, α and β, display high sequence homology to other complement and CTL pore-forming proteins. The third chain, C8γ, is covalently linked to C8α by a disulfide linkage; it is demonstrated that Cys40 of C8γ is linked to Cys164 of C8α, a unique cysteine located in a loop located between the cysteine-rich LDL-receptor class A module and the membrane-inserting region of C8α. C8γ was recently identified as a member of the lipocalin protein family, in which all proteins were either shown to, or are believed to bind small Hydrophobie ligands. The present results now demonstrate that C8γ incorporates retinol and retinoic acid in the presence of 2 M NaCl. Molecular modeling of C8γ, based on the crystal structure of the homologous β-lactoglobulin, reveals a structure of eight antiparallel beta-strands, bearing a highly hydrophobic binding pocket. The residues participating in the pocket formation are highly conserved when compared with the structures of β-lactoglobulin and retinol-binding protein, both of which are known to interact with retinol. It is therefore proposed that C8γ may act as a retinol transporting protein in plasma.