Functional analysis of the Hsp90-associated human peptidyl prolyl cis/trans isomerases FKBP51, FKBP52 and Cyp40.
Large peptidyl-prolyl cis/trans isomerases (PPIases) are important components of the Hsp90 chaperone complex. In mammalian cells, either Cyp40, FKBP51 or FKBP52 is incorporated into these complexes. It has been suggested that members of this protein family exhibit both prolyl isomerase and chaperone activity. Here we define the structural and functional properties of the three mammalian large PPIases. We find that in all cases two PPIase monomers bind to an Hsp90 dimer. However, the affinities of the PPIases are different with FKBP52 exhibiting the strongest interaction and Cyp40 the weakest. Furthermore, in the mammalian system, in contrast to the yeast system, the catalytic activity of prolyl isomerization corresponds well to that of the respective small PPIases. Interestingly, Cyp40 and FKBP51 are the more potent chaperones. Thus, it seems that both the affinity for Hsp90 and the differences in their chaperone properties, which may reflect their interaction with the non-native protein in the Hsp90 complex, are critical for the selective incorporation of a specific large PPIase.
Pirkl
F
F
Institut für Organische Chemie und Biochemie, Technische Universität München, Garching, 85747, Germany.
Buchner
J
J
D002151:Calorimetry; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D021983:Cyclophilins; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007536:Isomerism; D046911:Macromolecular Substances; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D020673:Protein Renaturation; D017433:Protein Structure, Secondary; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature; D013816:Thermodynamics; D017186:Titrimetry; D000099159:Tacrolimus Binding Protein 5; D000097322:Peptidyl-Prolyl Isomerase D
D002352:Carrier Proteins; D021983:Cyclophilins; D005656:Fungal Proteins; D018841:HSP90 Heat-Shock Proteins; D046911:Macromolecular Substances; D010455:Peptides; D019696:Peptidylprolyl Isomerase; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C403485:tacrolimus binding protein 4; C114456:PPID protein, human; D000097322:Peptidyl-Prolyl Isomerase D