Identification of functional domains in the plasma apolipoproteins by analysis of inter-species sequence variability.
Molecular evolution theory posits that sequence motifs essential for protein function are constrained by selective pressure from changing over long stretches of evolutionary time. Thus, analysis of inter-species amino acid sequence variability, by identifying highly conserved intervals, should predict the location of domains critical for protein function. We have analyzed the amino acid sequences of the mammalian apolipoproteins A-I, A-IV, C-I, C-II, C-III, D, and E with a computer algorithm that calculates numerical residue variability scores. The application of a median sieve filter to the data facilitated identification of the exact boundaries of highly conserved domains, which coincided with the location of known structural features and functional domains in this family of proteins. The analysis also identified highly conserved intervals in every apolipoprotein whose function is unknown at present, but which are candidates for regions with specific functional roles.
Weinberg
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Department of Internal Medicine, Bowman Gray School of Medicine, Winston-Salem, NC 27157.
D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry; D053302:Apolipoprotein C-I; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000097:blood / Q000737:chemistry*; D001054:Apolipoproteins A / Q000737:chemistry; D001056:Apolipoproteins C / Q000737:chemistry; D053399:Apolipoproteins D; D001057:Apolipoproteins E / Q000737:chemistry; D005075:Biological Evolution; D017124:Conserved Sequence; D006801:Humans; D018402:Manduca; D008969:Molecular Sequence Data; D010215:Papio; D010944:Plants; D017385:Sequence Homology; D013045:Species Specificity
D016632:Apolipoprotein A-I; D053302:Apolipoprotein C-I; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D053399:Apolipoproteins D; D001057:Apolipoproteins E; C022205:apolipoprotein A-IV