Dual-Family Peptidylprolyl Isomerases (Immunophilins) of Select Monocellular Organisms

Barik, Sailen

doi:10.3390/biom8040148

Cited by 10 publications

(14 citation statements)

References 54 publications

(113 reference statements)

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“…Although the structure of this region has not been experimentally determined, secondary and tertiary structure modeling did not reveal any helix. 12,13 Nevertheless, these proteins, expressed recombinantly, are highly soluble. 12,13 Thus, if a downstream companion helix is in fact needed for the solubility of 3TPR modules, the need may be context-dependent, such that in the absence of a companion helix, the presence of other domains in the protein or an abundance of hydrophilic amino acids in the TPR module itself may promote solubility.…”

Section: Discussionmentioning

confidence: 99%

Protein Tetratricopeptide Repeat and the Companion Non-tetratricopeptide Repeat Helices: Bioinformatic Analysis of Interhelical Interactions

Barik¹

2019

Bioinform Biol Insights

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The tetratricopeptide repeat (TPR) of proteins consists of a 34-amino acid, alpha-helical motif that comprises a pattern of small and large hydrophobic residues, leading to a recognizable signature sequence. Structural and functional studies have documented that tandem TPRs form a superhelix that interacts with client molecules through strategically placed amino acids. Interestingly, most of the known TPRs are flanked by alpha-helices that lack the TPR signature but often appear as a continuation of the TPR superhelix. The exact role and specificity of these TPR-accompanying non-TPR helices have remained a mystery. Here, starting with TPR proteins of known structure, bioinformatic analyses were conducted on these helices, which revealed that they are diverse in sequence, lacking a clear consensus. However, they display significant atomic contacts with the nearest TPR helix and, to some extent, with the next TPR helix over. The majority of these contacts do not use the signature residues of the TPR helix but rather involve hydrophobic side chains on the facing sides. Thus, compared with the TPR helices, these companion helices are generic in nature, and seem to serve as relatively passive gatekeepers, leaving the terminal TPR helices to encode the signature residues that interact with cognate clients.

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Section: Discussionmentioning

confidence: 99%

Protein Tetratricopeptide Repeat and the Companion Non-tetratricopeptide Repeat Helices: Bioinformatic Analysis of Interhelical Interactions

Barik¹

2019

Bioinform Biol Insights

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“…The module sequences are: [CyP]-[linker domain]-[FKBP] for CFBP, and [FKBP]-[3TPR]-[CyP] for FCBP. They also exhibit distinct organism preference, the CFBP being found in prokaryotes, and the FCBP in eukaryotes [9].…”

Section: Introductionmentioning

confidence: 99%

Biological Actions of the Hsp90-binding Immunophilins FKBP51 and FKBP52

et al. 2019

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Immunophilins are a family of proteins whose signature domain is the peptidylprolyl-isomerase domain. High molecular weight immunophilins are characterized by the additional presence of tetratricopeptide-repeats (TPR) through which they bind to the 90-kDa heat-shock protein (Hsp90), and via this chaperone, immunophilins contribute to the regulation of the biological functions of several client-proteins. Among these Hsp90-binding immunophilins, there are two highly homologous members named FKBP51 and FKBP52 (FK506-binding protein of 51-kDa and 52-kDa, respectively) that were first characterized as components of the Hsp90-based heterocomplex associated to steroid receptors. Afterwards, they emerged as likely contributors to a variety of other hormone-dependent diseases, stress-related pathologies, psychiatric disorders, cancer, and other syndromes characterized by misfolded proteins. The differential biological actions of these immunophilins have been assigned to the structurally similar, but functionally divergent enzymatic domain. Nonetheless, they also require the complementary input of the TPR domain, most likely due to their dependence with the association to Hsp90 as a functional unit. FKBP51 and FKBP52 regulate a variety of biological processes such as steroid receptor action, transcriptional activity, protein conformation, protein trafficking, cell differentiation, apoptosis, cancer progression, telomerase activity, cytoskeleton architecture, etc. In this article we discuss the biology of these events and some mechanistic aspects.

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“…Five of the previously identified domain combinations were ubiquitous to all oomycetes: FKBP (PF00254; oomcCYP03), GRX (PF00462; oomcCYP04), RRM (PF00076; oomcCYP05), WD40 repeat (PF00400; oomcCYP06), and U-box (PF04564; oomcCYP08) domains [26][27][28][29][30]. FKBP-3TPR-CYP bigram has been reported to be present in unicellular eukaryotes, including ciliophora, oomycetes, diatoms, and dinoflagellates, and as inhibiting calcineurin (protein phosphatase 2B) in the presence of the cognate drugs to exhibit family-specific drug sensitivity [31,32]. This bigram was detected in other stramenopiles and alveolates, but not from Rhizaria, Plantae, or opisthokonts (Supplementary Figure S1).…”

Section: Structure Analysismentioning

confidence: 99%

Genome-Wide Analysis of Cyclophilin Proteins in 21 Oomycetes

et al. 2019

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Cyclophilins (CYPs), a highly-conserved family of proteins, belong to a subgroup of immunophilins. Ubiquitous in eukaryotes and prokaryotes, CYPs have peptidyl-prolyl cis–trans isomerase (PPIase) activity and have been implicated as virulence factors in plant pathogenesis by oomycetes. We identified 16 CYP orthogroups from 21 diverse oomycetes. Each species was found to encode 15 to 35 CYP genes. Three of these orthogroups contained proteins with signal peptides at the N-terminal end, suggesting a role in secretion. Multidomain analysis revealed five conserved motifs of the CYP domain of oomycetes shared with other eukaryotic PPIases. Expression analysis of CYP proteins in different asexual life stages of the hemibiotrophic Phytophthora infestans and the biotrophic Plasmopara halstedii demonstrated distinct expression profiles between life stages. In addition to providing detailed comparative information on the CYPs in multiple oomycetes, this study identified candidate CYP effectors that could be the foundation for future studies of virulence.

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Dual-Family Peptidylprolyl Isomerases (Immunophilins) of Select Monocellular Organisms

Cited by 10 publications

References 54 publications

Protein Tetratricopeptide Repeat and the Companion Non-tetratricopeptide Repeat Helices: Bioinformatic Analysis of Interhelical Interactions

Protein Tetratricopeptide Repeat and the Companion Non-tetratricopeptide Repeat Helices: Bioinformatic Analysis of Interhelical Interactions

Biological Actions of the Hsp90-binding Immunophilins FKBP51 and FKBP52

Genome-Wide Analysis of Cyclophilin Proteins in 21 Oomycetes

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