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. 2004 Apr;134(4):1248-67.
doi: 10.1104/pp.103.031005. Epub 2004 Mar 26.

Immunophilins and parvulins. Superfamily of peptidyl prolyl isomerases in Arabidopsis

Zengyong He  1 , Legong Li, Sheng Luan
Affiliations

Immunophilins and parvulins. Superfamily of peptidyl prolyl isomerases in Arabidopsis

Zengyong He et al. Plant Physiol. 2004 Apr.

Abstract

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.

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Figures

Figure 1.
Figure 1.
Multiple sequence alignment of Arabidopsis FKBPs. Human FKBP12 (hFKBP12, GenBank accession no. A35780) was included for comparison. Amino acids of full length protein of single domain AtFKBPs were used for the alignment. Only the amino acids spanning the most conserved FKBP domain were used for the multiple domain AtFKBPs. The sequences used for the alignment were: amino acids 1 to 160 for AtFKBP42, 62, and 65; amino acids 237 to 378 for AtFKBP43; amino acids 350 to 477 for AtFKBP53; and amino acids 263 to 393 for AtFKBP72. The sequences were aligned using MegAlign followed by manual refinement. Consensus sequences (threshold 65%) were boxed and similar residues were shaded. Gaps (marked by dashes) were introduced to achieve maximum similarity. The amino acids necessary for rapamycin or FK506 binding as determined for hFKBP12 were marked by asterisks (*). The putative chloroplast/thylakoid targeting signal was manually adjusted around the double Arg or Lys-Arg residues (boxed). The hydrophobic stretches following the double Args were underlined. The α-helix and β-sheets derived from the hFKBP12 were shown.
Figure 2.
Figure 2.
Multiple sequence alignment of Arabidopsis CYPs. Human CyPA (hCyPA, GenBank accession no. A35780) was included for comparison. Amino acids of full-length protein of single domain AtCYPs were used for the alignment. Only the amino acids spanning the CYP domain of the multiple domain AtCYPs were used. The amino sequences used for the alignment were: amino acids 1 to 200 for AtCYP40, 57, 59, 63, and 95; amino acids 201 to 461 for AtCYP37; amino acids 201 to 437 for AtCYP38; amino acids 301 to 595 for AtCYP65, and amino acids 401 to 631 for AtCYP71. The sequences were aligned using MegAlign followed by manual refinement. Consensus sequences (threshold 65%) were boxed and similar residues were shaded. Gaps (marked by dashes) were introduced to achieve maximum similarity. The amino acids necessary for CsA binding as determined for hCyPA were marked by asterisk (*). The α-helix and β-sheets derived from the hCyPA were shown.
Figure 3.
Figure 3.
Chromosomal distribution of Arabidopsis immunophilins and parvulins on the five chromosomes. The chromosome number was indicated above each chromosome. Immunophilin and parvulin genes were located along the five chromosomes by Chromosome Map Tool and redrawn by Canvas 5.
Figure 4.
Figure 4.
Phylogenetic relationships of Arabidopsis FKBP (a) and CYP (b) proteins. The phylogenic analysis was based on the sequence alignments by ClustalX as described in “Materials and Methods.”
Figure 5.
Figure 5.
Domain architecture of the Arabidopsis FKBP family immunophilins. The beginning and ending amino acid numbers of each protein are shown at each end of the diagram. FKBP domains are represented by white box. The other functional domains such as tetratricopeptide repeats (TPR), charged domains, and Calmodulin-binding motif (CaM) are indicated separately. The transmembrane domains (TM) that are not part of the signal peptide are labeled. The bipartite chloroplast/thylakoid targeting signal, ER targeting signal, and the NLS are shown. The ER retention signals of AtFKBP15-1 (KNEL) and AtFKBP15-2 (NDEL) are noted. The numbers above the boxes denote the amino acid positions of the function domains.
Figure 6.
Figure 6.
Domain architecture of the Arabidopsis CYP family immunophilins. The beginning and ending amino acid numbers of each protein is shown at teach end of the diagram. CYP domains are represented by open box. The other functional domains such as tetratricopeptide repeats (TPR), U-box, WD repeats (WW), RRM, Leu-zipper, and zinc-finger are indicated. The transmembrane domains (TM) that are not part of the signal peptide are labeled. The bipartite chloroplast/thylakoid targeting signal, ER targeting signal, and the nucleus localization signal (NLS) are shown. The numbers above the boxes denote the amino acid positions of the function domains.
Figure 7.
Figure 7.
a, Multiple sequence alignment of Arabidopsis parvulins. Some members of the parvulin family from other organisms were used for comparison. They were: hPIN1 (human, Q13526), hPar14 (human, AB009690), ScESS1 (yeast, P22696), and EcPar10 (E. coli, P39159). Amino acids of full-length protein were used for the alignment. The sequences were aligned using MegAlign followed by manual refinement. Consensus sequences (threshold 65%) were boxed and similar residues were shaded. Gaps (marked by dashes) were introduced to achieve maximum similarity. The amino acids necessary for rapamycin or FK506 binding as determined for hFKBP12 were marked by asterisks. The α-helix and β-sheets derived from the hFKBP12 were shown. b, Phylogenetic relationships of Arabidopsis parvulin proteins and selected members of parvulin from other organisms. The phylogenic analysis was based on the sequence alignments by ClustalX as described in “Materials and Methods.” c, Domain architecture of the Arabidopsis parvulins. The beginning and ending amino acid numbers of each protein are shown at each end of the diagram. Parvulin PPIase domains are represented by white box. The Rhodanese domain of AtPIN3 is shaded and labeled. The chloroplast targeting signal is shown. The numbers above the boxes denote the amino acid positions of the function domains.
Figure 8.
Figure 8.
Expression patterns of Arabidopsis FKBP genes in different tissues. Semiquantitative RT-PCR was performed with gene specific primers using cDNAs synthesized from RNA samples isolated from different tissues. The tissues used were 3-d dark growing seedling (1), 3-d light growing seedling (2), 2-week seedling (3), leaves (4), caulin leaves (5), stems (6), flowers (7), and roots (8).
Figure 9.
Figure 9.
Expression patterns of Arabidopsis CYP proteins in different tissues. Semiquantitative RT-PCR was performed with gene specific primers using cDNAs synthesized from RNA samples isolated from different tissues. The tissues used were described in Figure 8.
Figure 10.
Figure 10.
Light response of the expression level of representative immunophilin genes as determined by semiquantitative RT-PCR. Six-day dark growing seedlings were exposed to light (100 μmol m−2 s−1) and tissues were harvested at the indicated time point. RNA isolation and RT-PCR was performed as detailed in “Materials and Methods.”
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References

    1. Abraham RT (1998) Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of cytokine receptor signaling. Curr Opin Immunol 10: 330–336 - PubMed
    1. Aldape RA, Futer O, DeCenzo MT, Jarrett BP, Murcko MA, Livingston DJ (1992) Charged surface residues of FKBP12 participate in formation of the FKBP12-FK506-calcineurin complex. J Biol Chem 267: 16029–16032 - PubMed
    1. Arpagaus S, Rawyler A, Braendle R (2002) Occurrence and characteristics of the mitochondrial permeability transition in plants. J Biol Chem 277: 1780–1787 - PubMed
    1. Azevedo C, Santos-Rosa MJ, Shirasu K (2001) The U-box protein family in plants. Trends Plant Sci 6: 354–358 - PubMed
    1. Bang H, Pecht A, Raddatz G, Scior T, Solbach W, Brune K, Pahl A (2000) Prolyl isomerases in a minimal cell. Catalysis of protein folding by trigger factor from Mycoplasma genitalium. Eur J Biochem 267: 3270–3280 - PubMed

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