Sequence diversification of the FK506-binding proteins in several different genomes.
Sequences of FK506-binding proteins (FKBPs) from four genomes of the following organisms were compared: the prokaryote Escherichia coli, the lower eukaryote Saccharomyces cerevisiae, the plant Arabidopsis thaliana, the nematode Caenorhabditis elegans and a composite of 14 unique FKBPs from two mammalian organisms Homo sapiens (man) and Mus musculus (domestic mouse). A singular FK506-like binding domain (FKBD) has about 12 kDa and occurs in the form of archetypal FKBP-12 and as a part of different proteins ranging in size from 13 to 135 kDa. Some organisms may contain a variable number of proteins 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 fall to about 30% for pairwise sequence comparisons of mammalian and bacterial FKBPs-12 which suggests that their sequences are divergent. Multiple sequence alignment of FKBPs from the four genomes and a set of unique mammalian FKBPs does not contain any explicit consensus sequence but certain sequence positions have conserved physico-chemical characteristics. Variations of hydrophobicity and bulkiness in the multiple sequence alignment are nonsymmetrical because the physico-chemical properties of the aligned sequences changed during evolution. These variations at the sequence positions which are crucial for binding the immunosuppressive macrolide FK506 and peptidyl-prolyl cis/trans isomerase (PPIase) activity are small.
Département d'Ingénierie et d'Etudes des Protéines, DSV/CEA, CE-Saclay, Gif-sur-Yvette, France.
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D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics; D003196:Computer Graphics; D016208:Databases, Factual; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D020104:Immunophilins / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000235:genetics; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D022021:Tacrolimus Binding Proteins
D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D019696:Peptidylprolyl Isomerase