Structural and functional characterization of complement C8 gamma, a member of the lipocalin protein family.
Human complement component C8 exhibits an unusual structure in that it contains three chains, two of which, alpha and beta, display high sequence homology to other complement and CTL pore-forming proteins. The third chain, C8 gamma, is covalently linked to C8 alpha by a disulfide linkage; it is demonstrated that Cys40 of C8 gamma is linked to Cys164 of C8 alpha, a unique cysteine located in a loop located between the cysteine-rich LDL-receptor class A module and the membrane-inserting region of C8 alpha. C8 gamma 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 hydrophobic ligands. The present results now demonstrate that C8 gamma incorporates retinol and retinoic acid in the presence of 2 M NaCl. Molecular modeling of C8 gamma, based on the crystal structure of the homologous beta-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 beta-lactoglobulin and retinol-binding protein, both of which are known to interact with retinol. It is therefore proposed that C8 gamma may act as a retinol transporting protein in plasma.
Haefliger
J A
JA
Institute of Biochemistry, University of Lausanne, Switzerland.
Peitsch
M C
MC
Jenne
D E
DE
Tschopp
J
J
D000510:Alpha-Globulins / Q000737:chemistry; D000595:Amino Acid Sequence; D003185:Complement C8 / Q000737:chemistry* / Q000378:metabolism; D003488:Cyanogen Bromide / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D007782:Lactoglobulins / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010446:Peptide Fragments / Q000737:chemistry; D012177:Retinol-Binding Proteins / Q000737:chemistry; D054839:Retinol-Binding Proteins, Plasma; D012997:Solvents; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism
D000510:Alpha-Globulins; D003185:Complement C8; D004220:Disulfides; D007782:Lactoglobulins; D008024:Ligands; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D012997:Solvents; C016001:alpha-1-microglobulin; D014801:Vitamin A; D014212:Tretinoin; D003488:Cyanogen Bromide