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On the role, ecology, phylogeny, and structure of dual-family immunophilins

Cell Stress and Chaperones volume 22, pages 833–845 (2017)Cite this article

Abstract

The novel class of dual-family immunophilins (henceforth abbreviated as DFI) represents naturally occurring chimera of classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker that may include a three-unit tetratricopeptide (TPR) repeat. Here, I report a comprehensive analysis of all current DFI sequences and their host organisms. DFIs are of two kinds: CFBP (cyclosporin- and FK506-binding protein) and FCBP (FK506- and cyclosporin-binding protein), found in eukaryotes. The CFBP type occurs in select bacteria that are mostly extremophiles, such as psychrophilic, thermophilic, halophilic, and sulfur-reducing. Essentially all DFI organisms are unicellular. I suggest that DFIs are specialized bifunctional chaperones that use their flexible interdomain linker to associate with large polypeptides or multisubunit megacomplexes to promote simultaneous folding or renaturation of two clients in proximity, essential in stressful and denaturing environments. Analysis of sequence homology and predicted 3D structures of the FKBP and CYN domains as well as the TPR linkers upheld the modular nature of the DFIs and revealed the uniqueness of their TPR domain. The CFBP and FCBP genes appear to have evolved in parallel pathways with no obvious single common ancestor. The occurrence of both types of DFI in multiple unrelated phylogenetic clades supported their selection in metabolic and environmental niche roles rather than a traditional taxonomic relationship. Nonetheless, organisms with these rare immunophilins may define an operational taxonomic unit (OTU) bound by the commonality of chaperone function.

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Abbreviations

CYN:

Cyclophilin;

CFBP:

Cyclosporin- and FK506-binding protein

FCBP:

FK506- and cyclosporin-binding protein

DFI:

Dual-family immunophilin

Hsp:

Heat shock protein

OTU:

Operational taxonomic unit

TPR:

Tetratricopeptide repeat

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Acknowledgements

I am deeply indebted to two research groups for generously sharing their raw datasets: Professor Lynne Regan (Yale University, New Haven, CT) and her associate, Dr. Jieming Chen (currently in the Institute for Computational Health Sciences, University of California, San Francisco), for sharing the TPR sequence collection used in their analysis (Sawyer et al. 2013), and Dr. Stilianos Louca (University of British Columbia, Canada) for sharing the list of the organisms from their OTU studies (Louca et al. 2016). I thank Professor Andreas Teske (Marine Sciences, University of North Carolina, Chapel Hill, NC) for helpful discussions on the phylogeny and ecology of DFI organisms.

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    Sailen Barik

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Barik, S. On the role, ecology, phylogeny, and structure of dual-family immunophilins. Cell Stress and Chaperones 22, 833–845 (2017). https://doi.org/10.1007/s12192-017-0813-x

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Keywords

  • Chaperone
  • Immunophilin
  • Apicomplexa
  • Extremophiles
  • Flavobacteria
  • Spirochetes