Identification of Eukaryotic Parvulin Homologues: A New Subfamily of Peptidylprolyl cis–trans Isomerases

Rulten, Stuart L.; Thorpe, Julian R.; Kay, John E.

doi:10.1006/bbrc.1999.0828

Cited by 46 publications

(51 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The degree of homology to the PPIase domains of other Pin1-like enzymes were found to be 53% with hPin1 (accession number Q13526 (21)), 51% with Ptf1 from S. cerevisiae (accession number P22696 (14,15)) and SspI from N. crassa (accession number AJ0006023 (20)), respectively, and 47% with Dodo from D. melanogaster (accession number P54353 (18)). Less sequence homology exists to other parvulins with rather unspecific substrate recognition pattern including hPar14 with 28% identity (accession number AB009690 (34,35)) and ECPar10 from E. coli (accession number P39159 (36, 37)) with 32% identity to DlPar13. In both enzymes some amino acid residues of the supposed substrate binding pocket differ from the conserved region of the phosphorylation-specific proteins as illustrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

Functional Replacement of the Essential ESS1 in Yeast by the Plant Parvulin DlPar13

Metzner

Stoller

Rücknagel

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

A functionally Pin1-like peptidyl-prolyl cis/trans isomerase (PPIase 1 ) was isolated from proembryogenic masses (PEMs) of Digitalis lanata according to its enzymatic activity. Partial sequence analysis of the purified enzyme (DlPar13) revealed sequence homology to members of the parvulin family of PPIases. Similar to human Pin1 and yeast Ess1, it exhibits catalytic activity toward substrates containing (Thr(P)/Ser(P))-Pro peptide bonds and comparable inhibition kinetics with juglone. Unlike Pin1-type enzymes it lacks the phosphoserine or phosphothreonine binding WW domain. Western blotting with anti-DlPar13 serum recognized the endogenous form in nucleic and cytosolic fractions of the plant cells. Since the PIN1 homologue ESS1 is an essential gene, complementation experiments in yeast were performed. When overexpressed in Saccharomyces cerevisiae DlPar13 is almost as effective as hPin1 in rescuing the temperature-sensitive phenotype caused by a mutation in ESS1. In contrast, the human parvulin hPar14 is not able to rescue the lethal phenotype of this yeast strain at nonpermissive temperatures. These results suggest a function for DlPar13 rather similar to parvulins of the Pin1-type.Human Pin1 belongs to the parvulin family of peptidyl-prolyl cis/trans isomerases (EC 5.2

show abstract

Section: Resultsmentioning

confidence: 99%

Functional Replacement of the Essential ESS1 in Yeast by the Plant Parvulin DlPar13

Metzner

Stoller

Rücknagel

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In this review the three groups of PPIases which are encoded in the human genome were analyzed, namely cyclophilins, hPin1 with its paralogue hParv14 [13][14], and the FKBP family of proteins. Because some members of the last family of proteins are plausible targets for a variety of pharmacological-relevant molecules we emphasized in somewhat greater detail their physico-chemical and biochemical properties.…”

Section: Superfamily Of Ppiasesmentioning

confidence: 99%

“…The gene of a shorter mammalian variant of Pin1 protein (hPar14), which is devoid of the WW domain is encoded on human chromosome 1p31 [19][20]. Recombinant hPar14 preferentially accelerates cis/trans isomerization of Arg-Pro epitopes in synthetic peptides [13][14].…”

Section: The Pin1 Family Of Proteinsmentioning

confidence: 99%

Peptidylprolyl Cis / Trans Isomerases (Immunophilins): Biological Diversity - Targets - Functions

Gałat

2003

CTMC

342

302

View full text Add to dashboard Cite

Information recovered from genome sequencing projects, multiple sequence alignments, structural analyses of PPIase and published records were used in deciphering the biological diversity, functions and targets of four groups of proteins encoded by dissimilar sets of sequences whose spatial representations exhibit peptidylprolyl cis/trans isomerase activity (PPIase). In the human genome there are encoded fifteen proteins whose segments have significant homology with the sequence of 12 kDa protein which is the target of the potent immunosuppressive macrolides FK506 or rapamycin. The 12 kDa archetype of the FK506-binding protein (FKBP), known as FKBP-12a, is an abundant intracellular protein whereas other FKBPs possessing from one to four FK506-like binding domains (FKBDs) have nominal masses varying from 13 to 135 kDa. The human genome contains at least sixteen genes encoding proteins comprising one cyclosporin-A (CsA) binding domain (CLD) called cyclophilins whose nominal masses vary from 17 to 324 kDa and multiple coding segments for small cyclophilins (17-19 kDa) whose transcription levels and functions remain unknown. The third group of PPIases encoded in the genome comprises two proteins (hPin1 and hParv14) where hPin1 is an important PPIase for cell cycle. The A. thaliana, C. elegans, D. melanogaster and S. cerevisiae genomes encode a less diverse spectrum of PPIases whereas the prokaryotic genomes contain from none to three cyclophilins, from none to four genes encoding FKBPs, one distant homologue of the Pin1 protein named parvulin and the fourth group of PPIases known as trigger factors. PPIases are discretely distributed to different cellular compartments and interact with a number of targets that control a range of cellular processes. Analyses of the sequence alignments of the two groups of PPIases, namely cyclophilins and FKBPs from diverse phyla, show that in each group their sequences diverge but the amino acid residues which form the PPIase activity site and macrolide binding cavity remain well conserved in the majority of them which suggests that the spatial structures and functions of each group of PPIases remain conserved.

show abstract

“…However, it still retains the phospho-substrate specificity and can complement yeast mutant lacking ESS1 (Landrieu et al, 2000;Metzner et al, 2001;Yao et al, 2001). The activity of the other human parvulin, hPar14, is independent from substrate phosphorylation (Rulten et al, 1999;Uchida et al, 1999). It was shown that phosphorylation of the N-terminal domain of hPar14 regulates its subcellular localization and DNA binding (Reimer et al, 2003).…”

mentioning

confidence: 99%

Immunophilins and Parvulins. Superfamily of Peptidyl Prolyl Isomerases in Arabidopsis

2004

View full text Add to dashboard Cite

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...

show abstract

Identification of Eukaryotic Parvulin Homologues: A New Subfamily of Peptidylprolyl cis–trans Isomerases

Cited by 46 publications

References 21 publications

Functional Replacement of the Essential ESS1 in Yeast by the Plant Parvulin DlPar13

Functional Replacement of the Essential ESS1 in Yeast by the Plant Parvulin DlPar13

Peptidylprolyl Cis / Trans Isomerases (Immunophilins): Biological Diversity - Targets - Functions

Immunophilins and Parvulins. Superfamily of Peptidyl Prolyl Isomerases in Arabidopsis

Contact Info

Product

Resources

About