Variations of sequences and amino acid compositions of proteins that sustain their biological functions: An analysis of the cyclophilin family of proteins

The sequences of the ubiquitous and phylogenetically diversified cyclophili n family of proteins were divided into six groups, namely, vertebrates, inv ertebrates, other metazoa, plants, fungi, and prokaryotes. These groups of sequences were aligned with the multiple sequence alignment program Clustal -W. The variations of amino acid substitutions and amino acid compositions for these six groups of cyclophilins were calculated using a novel suite of multiple-sequence alignment analysis routines. The cyclophilins from verte brates can be divided for at least two distinct structural classes that dif fer from each other by a variable-length amino acid insert within the loop that links alpha-helix II and beta-strand III. A similar structural feature is also present in the other groups of cyclophilins, namely, those from in vertebrates, other metazoa, plants, and fungi. The sequences of cyclophilin s from fungi and prokaryotes are more diversified than those from vertebrat es, and their alterations involve structures other than the amino acid inse rts within the loops. Variations of the hydrophobicity and bulkiness of ami no acid substitutions of the aligned sequences were calculated for each gro up of cyclophilins and for the alignment of all the sequences. The variatio ns have clear asymmetry that may signify the need for modification of the p hysical properties of certain fragments of cyclophilins that are involved i n interactions with various cellular components in the evolving environment . (C) 1999 Academic Press.