Comparative analysis of repeated sequences in rat apolipoproteins A-I, A-IV, and E.
To understand the structural, functional, and evolutionary relationships among the principal protein components of rat high density lipoprotein particles, we undertook a systematic comparative analysis of the primary structures of apolipoproteins (apo)-A-I, -A-IV, and -E. Human apo-A-I and rat apo-A-IV have been shown previously to contain repeated sequences that presumably arose by intragenic duplication of 11- or 22-amino acid amphipathic segments. For apo-A-I, these segments are thought to be the structures responsible for lipid binding and activation of lecithin:cholesterol acyltransferase. From an analysis of the sequence of a full-length cDNA clone, rat apo-A-I is shown to contain eight tandem repetitions of a 22-amino acid segment. However, compared with human apo-A-I, the rat protein has undergone three deletions, two of which involve multiple amino acids in the repeated sequence domain. This disruption of the periodic structure of the protein raises the possibility of species-specific variation in the ability of rat apo-A-I to interact with high density lipoproteins and activate lecithin:cholesterol acyltransferase. Statistical analysis of the structure and organization of repeated sequences in apo-A-I, -A-IV, and -E demonstrates that all three proteins are paralogous members of a dispersed gene family. Despite overall similarity in sequence organization, different portions of these sequences have evolved at different rates. Diversification of a duplicated ancestral sequence has resulted in three lipid-binding proteins with distinct and shared functions.
D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D006801:Humans; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D013045:Species Specificity
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001057:Apolipoproteins E; C022205:apolipoprotein A-IV; D004247:DNA