IDENTIFICATION OF FUNCTIONAL DOMAINS IN THE PLASMA APOLIPOPROTEINS BYANALYSIS OF INTERSPECIES SEQUENCE VARIABILITY

Molecular evolution theory posits that sequence motifs essential for p rotein function are constrained by selective pressure from changing ov er long stretches of evolutionary time. Thus, analysis of inter-specie s amino acid sequence variability, by identifying highly conserved int ervals, should predict the location of domains critical for protein fu nction. We have analyzed the amino acid sequences of the mammalian apo lipoproteins A-T, A-IV, C-I, C-II, C-III, D, and E with a computer alg orithm that calculates numerical residue variability scores. The appli cation 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 conser ved intervals in every apolipoprotein whose function is unknown at pre sent, but which are candidates for regions with specific functional ro les.