Haefliger J A, Peitsch M C, Jenne D E, Tschopp J
Institute of Biochemistry, University of Lausanne, Switzerland.
Mol Immunol. 1991 Jan-Feb;28(1-2):123-31. doi: 10.1016/0161-5890(91)90095-2.
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.
人类补体成分C8呈现出一种不同寻常的结构，它包含三条链，其中两条链，即α链和β链，与其他补体及细胞毒性T淋巴细胞（CTL）的成孔蛋白具有高度的序列同源性。第三条链，C8γ链，通过二硫键与C8α链共价相连；已证实C8γ链的半胱氨酸40与C8α链的半胱氨酸164相连，C8α链中的这个独特半胱氨酸位于富含半胱氨酸的低密度脂蛋白受体A类模块与C8α链的膜插入区域之间的一个环中。C8γ链最近被鉴定为脂质运载蛋白家族的成员，该家族中的所有蛋白质要么已被证明，要么被认为能结合小的疏水性配体。目前的研究结果表明，在2M氯化钠存在的情况下，C8γ链能结合视黄醇和视黄酸。基于同源β-乳球蛋白晶体结构的C8γ链分子模型显示，它具有由八条反平行β链组成的结构，带有一个高度疏水的结合口袋。与已知能与视黄醇相互作用的β-乳球蛋白和视黄醇结合蛋白的结构相比，参与口袋形成的残基高度保守。因此，有人提出C8γ链可能在血浆中充当视黄醇转运蛋白。
