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Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl‐prolyl cis‐trans isomerases
Author(s) -
Trandinh C. Christine,
Pao Gerald M.,
Saier Milton H.
Publication year - 1992
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.6.15.1464374
Subject(s) - cis trans isomerases , prolyl isomerase , peptidylprolyl isomerase , isomerase , biology , evolutionary biology , stereochemistry , chemistry , pin1 , genetics , gene
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, C. C., Pao, G. M., Saier, M. H., Jr. Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl‐prolyl cis‐trans isomerases. FASEB J. 6: 3410‐3420; 1992.