PRESENCE OF AN EXTENDED DUPLICATION IN THE PUTATIVE LOW-DENSITY-LIPOPROTEIN RECEPTOR-BINDING DOMAIN OF APOLIPOPROTEIN-B - CLONING AND CHARACTERIZATION OF THE DOMAIN IN SALMON

The sequence of the C-terminal 1058 amino acids of atlantic salmon (Sa lmo salar) apolipoprotein (apo) B was deduced from the nucleotide sequ ence of cloned cDNA. In comparison with chicken or mammals apoB-100, s almon apoB is C-terminally truncated and extended gaps are found. The two clusters of positively charged residues, previously identified as part of the putative low-density-lipoprotein (LDL) receptor-binding do main of apoB, are brought into close proximity in salmon apoB. This is achieved by the absence between the two clusters of the proline-rich area with the potential to form an amphipathic beta sheet, present in higher vertebrates. In addition, analysis of apoB amino acid sequences currently available in vertebrates revealed the presence of an extend ed internal duplication in the putative LDL receptor-binding domain. T hus, the two basic clusters would have been duplicated resulting in th e presence, except for salmon apoB, of two homologous sites in the C-t erninal part of the molecule. The results described here together with earlier biochemical and genetic evidence support the view that Arg350 0, a residue mutated in familial defective apoB-100, could be included in a folded critical region of the putative LDL receptor-binding doma in of human apoB-100. This region possibly brings the two sub-domains that arise from the duplication close to each other.