TAXONOMY OF NUCLEAR RECEPTORS AND SERPINS BY MULTIVARIATE-ANALYSIS OFAMINO-ACID-COMPOSITION

The global amino-acid composition of a protein, although a cruder vari able than sequence, is nevertheless informative and has been correlate d with protein structural class. In the present study, we have applied complementary multivariate methods based on chi(2)-metrics (correspon dence factor analysis (CFA), minimum spanning tree (MST), ascending hi erarchical classification (AHC)) to the analysis of the amino-acid fre quency patterns of the C-terminal domain of 39 members of the nuclear receptor superfamily. The correlations we observed among receptors by this simple approach were, with few exceptions, in line with published phylogenetic dendrograms derived by sequence alignment. Further multi variate analyses were performed on the receptor population combined wi th 26 serine protease inhibitors (SERPINS) in view of the analogies de tected between these superfamilies by hydrophobic cluster analysis (HC A), which were at the origin of the choice of alpha 1-antitrypsin as a 3-dimensional (3D) model for the receptor hormone-binding domain. Bot h the MST and AHC identified two distinct protein populations which in the principal phi(1) phi(2) CFA plot showed virtually mo overlap, thu s suggesting that receptors and SERPINS have different overall folding patterns, although the lower-order phi(3) phi(4) plot did reveal some similarities, essentially in the use of hydrophobic amino acids, that might account for analogies in HCA patterns. Receptors had a preferen ce for those amino acids that are more frequent in alpha-helices and S ERPINS for those in beta-strands and also tended to use different amin o acids in turns. We therefore propose that multivariate analysis of a mino-acid composition may prove helpful in identifying proteins for su bsequent HCA. Copyright (C) 1996 Elsevier Science Ltd.