title: The chaperone function of cyclophilin 40 maps to a cleft between the prolyl isomerase and tetratricopeptide repeat domains.
abstract: Cyclophilin 40 (CyP40), an immunophilin cochaperone present in steroid receptor-Hsp90 complexes, contains an N-terminal peptidylprolyl isomerase (PPIase) domain separated from a C-terminal Hsp90-binding tetratricopeptide repeat (TPR) domain by a 30-residue linker. To map CyP40 chaperone function, CyP40 deletion mutants were prepared and analysed for chaperone activity. CyP40 fragments containing the PPIase domain plus linker or the linker region and the adjoining TPR domain retained chaperone activity, whilst individually, the catalytic and TPR domains were devoid of chaperoning ability. CyP40 chaperone function then, is localized within the linker that forms a binding cleft with potential to accommodate non-native substrates.
authors.affiliation: Laboratory for Molecular Endocrinology, Western Australian Institute for Medical Research and UWA Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Mok
authors.forename: Rudi K
authors.initials: RK
authors.lastname: Allan
authors.forename: Amerigo
authors.initials: A
authors.lastname: Carrello
authors.forename: Kiran
authors.initials: K
authors.lastname: Wangoo
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Walkinshaw
authors.forename: Thomas
authors.initials: T
authors.lastname: Ratajczak
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D017124:Conserved Sequence; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D010455:Peptides; D021983:Cyclophilins