GENOMIC STRUCTURE OF THE HUMAN-COMPLEMENT PROTEIN C8-GAMMA - HOMOLOGYTO THE LIPOCALIN GENE FAMILY

Human C8 is one of five complement components (C5b, C6, C7, C8, C9) th at interact to form the cytolytic C5b-9 complex on target cells. It co ntains three subunits (C8 alpha, C8 beta, C8 gamma) which are encoded in separate genes. In relation to other proteins of the complement sys tem, C8 gamma is unusual in that it is not structurally related to any other component nor does it have an obvious function. Based on weak b ut significant sequence similarity, it is proposed to be a member of t he lipocalin family of widely distributed proteins that bind and trans port small hydrophobic ligands. In this study, the human C8 gamma gene has been characterized and found to contain seven exons spanning simi lar to 1.8 kb. S1 nuclease and anchored PCR were used to identify the transcription initiation site. This site is preceded by putative regul atory elements that include two SP1 binding sites, several glucocortic oid response elements, and two SV40 enhancer core consensus sequences. A comparison to genes of other lipocalins reveals a remarkably close correlation in exon number, lengths, and phases. A close correspondenc e in exon boundaries is also observed and suggests that C8 gamma conta ins the same discrete structural elements that define the characterist ic beta-barrel shape of the lipocalins. These results establish that C 8 gamma is indeed ancestrally related to the lipocalin family and stre ngthens the likelihood that its role in the complement system is to bi nd an as yet unidentified ligand.