Confirmation of the existence of a third family among peptidyl‐prolyl <i>cis/trans</i> isomerases Amino acid sequence and recombinant production of parvulin

Rahfeld, Jens; Rücknagel, Karl Peter; Schelbert, Birte; Ludwig, Birgit; Hacker, Jörg; Mann, Karlheinz; Fischer, Gunter

doi:10.1016/0014-5793(94)00932-5

Cited by 190 publications

(171 citation statements)

References 26 publications

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“…In addition to the cyclophilins, two other families of PPIs have been described, the FK506-binding proteins (FKBPs) (Harding et al, 1989;Siekierka et al, 1989) and parvulins (Rahfeld et al, 1994), both structurally unrelated to the cyclophilins. In spite of this, it has been shown that overexpression of cyclophilin A can rescue a lethal parvulin mutant in yeast (ArevaloRodriguez et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Positional cloning identifies a novel cyclophilin as a candidate amplified oncogene in 1q21

et al. 2002

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Gains of 1q21-q23 have been associated with metastasis and chemotherapy response, particularly in bladder cancer, hepatocellular carcinomas and sarcomas. By positional cloning of ampli®ed genes by yeast arti®cial chromosome-mediated cDNA capture using magnetic beads, we have identi®ed three candidate genes (COAS1, -2 and -3) in the ampli®ed region in sarcomas. COAS1 and -2 showed higher ampli®cation levels than COAS3. Most notably, ampli®cation was very common in osteosarcomas, where in particular COAS2 was highly expressed. COAS1 has multiple repeats and shows no homology to previously described genes, whereas COAS2 is a novel member of the cyclosporin-binding peptidylprolyl isomerase family, very similar to cyclophilin A. COAS2 was overexpressed almost exclusively in aggressive metastatic or chemotherapy resistant tumours. Although COAS2 was generally more ampli®ed than COAS1, it was not expressed in well-di erentiated liposarcomas, where ampli®cation of this region is very common. All three genes were found to be ampli®ed and over-expressed also in breast carcinomas. The complex nature of the 1q21-23 amplicons and close proximity of the genes make unequivocal determination of the gene responsible di cult. Quite likely, the di erent genes may give selective advantages to di erent subsets of tumours.

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Section: Discussionmentioning

confidence: 99%

Positional cloning identifies a novel cyclophilin as a candidate amplified oncogene in 1q21

et al. 2002

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“…A parvulin protein was originally found in Escherichia coli as a novel PPIase that consists of only 92 amino acids and is hence named parvulin (Latin: parvulus, very small; Rahfeld et al, 1994). Later on, parvulin homologs were found in both prokaryotic and eukaryotic organisms like SurA from E. coli (Eisenstark et al, 1992), Ess1/Ptf1 from yeast (Saccharomyces cerevisiae; Hanes et al, 1989;Hani et al, 1995), and Pin1 from human (Lu et al, 1996).…”

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confidence: 99%

Immunophilins and Parvulins. Superfamily of Peptidyl Prolyl Isomerases in Arabidopsis

2004

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Immunophilins are defined as receptors for immunosuppressive drugs including cyclosporin A, FK506, and rapamycin. The cyclosporin A receptors are referred to as cyclophilins (CYPs) and FK506-and rapamycin-binding proteins are abbreviated as FKBPs. These two groups of proteins (collectively called immunophilins) share little sequence homology, but both have peptidyl prolyl cis/trans isomerase (PPIase) activity that is involved in protein folding processes. Studies have identified immunophilins in all organisms examined including bacteria, fungi, animals, and plants. Nevertheless, the physiological function of immunophilins is poorly understood in any organism. In this study, we have surveyed the genes encoding immunophilins in Arabidopsis genome. A total of 52 genes have been found to encode putative immunophilins, among which 23 are putative FKBPs and 29 are putative CYPs. This is by far the largest immunophilin family identified in any organism. Both FKBPs and CYPs can be classified into single domain and multiple domain members. The single domain members contain a basic catalytic domain and some of them have signal sequences for targeting to a specific organelle. The multiple domain members contain not only the catalytic domain but also defined modules that are involved in protein-protein interaction or other functions. A striking feature of immunophilins in Arabidopsis is that a large fraction of FKBPs and CYPs are localized in the chloroplast, a possible explanation for why plants have a larger immunophilin family than animals. Parvulins represent another family of PPIases that are unrelated to immunophilins in protein sequences and drug binding properties. Three parvulin genes were found in Arabidopsis genome. The expression of many immunophilin and parvulin genes is ubiquitous except for those encoding chloroplast members that are often detected only in the green tissues. The large number of genes and diversity of structure domains and cellular localization make PPIases a versatile superfamily of proteins that clearly function in many cellular processes in plants.Immunosuppressive drugs cyclosporin A (CsA), FK506, and rapamycin are used clinically in transplantation to prevent graft rejection. During the course to understand the molecular mechanisms of immunosuppression by CsA, FK506, and rapamycin, the cellular receptors of these drugs have been purified and characterized (Schreiber, 1991;Fruman et al., 1994). CsA binds to a family of receptors named cyclophilins (CyPs), and FK506 and rapamycin bind to a distinct set of receptors called FKBPs (FK506 and rapamycin-binding proteins). Cyclophilins and FKBPs are collectively referred to as immunophilins (Schreiber, 1991).The complexes formed by immunophilins and their cognate ligands are the functional modules for immunosuppression. The FKBP12-FK506 and CyPCsA complexes, but not their separate components, bind to and inhibit the activity of calcineurin, a Ca 21 , calmodulin-dependent protein phosphatase (Liu et al., 1991). Studies have demonstrated that inhib...

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“…We have previously identified in Bacillus subtilis a membrane-bound lipoprotein, PrsA, which according to sequence similarity belongs to the parvulin family of PPIases (18). In PrsA a stretch of 90 amino acids is 45% identical with E. coli parvulin.…”

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confidence: 99%

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

Vitikainen

Lappalainen

Seppälä

et al. 2004

Journal of Biological Chemistry

118

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The PrsA protein of Bacillus subtilis is an essential membrane-bound lipoprotein that is assumed to assist post-translocational folding of exported proteins and stabilize them in the compartment between the cytoplasmic membrane and cell wall. This folding activity is consistent with the homology of a segment of PrsA with parvulin-type peptidyl-prolyl cis/trans isomerases (PPIase). In this study, molecular modeling showed that the parvulin-like region can adopt a parvulin-type fold with structurally conserved active site residues. PrsA exhibits PPIase activity in a manner dependent on the parvulin-like domain. We constructed deletion, peptide insertion, and amino acid substitution mutations and demonstrated that the parvulin-like domain as well as flanking N-and C-terminal domains are essential for in vivo PrsA function in protein secretion and growth. Surprisingly, none of the predicted active site residues of the parvulin-like domain was essential for growth and protein secretion, although several active site mutations reduced or abolished the PPIase activity or the ability of PrsA to catalyze proline-limited protein folding in vitro. Our results indicate that PrsA is a PPIase, but the essential role in vivo seems to depend on some non-PPIase activity of both the parvulin-like and flanking domains.

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Confirmation of the existence of a third family among peptidyl‐prolyl cis/trans isomerases Amino acid sequence and recombinant production of parvulin

Cited by 190 publications

References 26 publications

Positional cloning identifies a novel cyclophilin as a candidate amplified oncogene in 1q21

Positional cloning identifies a novel cyclophilin as a candidate amplified oncogene in 1q21

Immunophilins and Parvulins. Superfamily of Peptidyl Prolyl Isomerases in Arabidopsis

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

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