Sequence diversification of the FK506-binding proteins in several different genomes

Sequences of FK506-binding proteins (FKBPs) from four genomes of the follow ing organisms were compared: the prokaryote Escherichia coli, the lower euk aryote Saccharomyces cerevisiae, the plant Arabidopsis thaliana, the nemato de Caenorhabditis elegans and a composite of 14 unique FKBPs from two mamma lian organisms Homo sapiens (man) and Mus musculus (domestic mouse). A sing ular FK506-like binding domain (FKBD) has about 12 kDa and occurs in the fo rm of archetypal FKBP-12 and as a part of different proteins ranging in siz e from 13 to 135 kDa. Some organisms may contain a variable number of prote ins which consist from two to four consecutively fused FKBDs. In the 12-kDa subgroup of archetypal FKBPs sequence identity (ID) varies from 100 to 83% (mammalian FKBPs-12), 75-50% in mammalian vs. invertebrate FKBPs-12, and f all to about 30% for pairwise sequence comparisons of mammalian and bacteri al FKBPs-12 which suggests that their sequences are divergent. Multiple seq uence alignment of FKBPs from the four genomes and a set of unique mammalia n FKBPs does not contain any explicit consensus sequence but certain sequen ce positions have conserved physico-chemical characteristics. Variations of hydrophobicity and bulkiness in the multiple sequence alignment are nonsym metrical because the physico-chemical properties of the aligned sequences c hanged during evolution. These variations at the sequence positions which a re crucial for binding the immunosuppressive macrolide FK506 and peptidyl-p rolyl cis/trans isomerase (PPIase) activity are small.