Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl-prolyl cis-trans isomerases.
The immunophilins, protein receptors for the immunosuppressing drugs cyclosporin A and FK506 and related proteins from plants, fungi, and bacteria, have been analyzed structurally and evolutionarily. The cyclosporin A binding proteins (cyclophilins) represent one ubiquitous family of homologous proteins, and the FK506- and rapamycin-binding proteins (FKBPs) constitute a second, unrelated family. Multiple sequence alignments of members of each of these two protein families define the highly conserved residues that are likely to play important structural and functional roles, and mutations in representative members of these two families that abolish or alter function have been evaluated. FKBPs have undergone greater evolutionary divergence than the cyclophilins. Evolutionary trees were constructed using two distinct programs, and these trees establish the structural relationships that allow division of each of these families into subgroups. The results lead to the suggestion that several genes encoding isozymic forms of the FKBPs and possibly also of the cyclophilins existed in prokaryotes before the emergence of eukaryotes on earth and that representatives of these genes were transmitted to both kingdoms to give rise to current subfamilies of these proteins. By contrast, compartmentalization of both classes of immunophilins appears to have arisen independently in prokaryotes and eukaryotes, late in evolutionary history.
Trandinh
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CC
Department of Biology, University of California at San Diego, La Jolla 92093-0116.
Pao
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GM
Saier
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MH
D000591:Amino Acid Isomerases / Q000737:chemistry / Q000145:classification* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002352:Carrier Proteins / Q000737:chemistry / Q000145:classification* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019696:Peptidylprolyl Isomerase; D010802:Phylogeny; D011971:Receptors, Immunologic / Q000737:chemistry / Q000145:classification* / Q000235:genetics; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D011971:Receptors, Immunologic; C028752:cyclosporin receptor; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase