TurboID mapping reveals the exportome of secreted intrinsically disordered proteins in the transforming parasite Theileria annulata.

Brühlmann, Francis; Perry, Carmen; Griessen, Charlotte; Gunasekera, Kapila; Reymond, Jean-Louis; Naguleswaran, Arunasalam; Rottenberg, Sven; Woods, Kerry; Olias, Philipp (2024). TurboID mapping reveals the exportome of secreted intrinsically disordered proteins in the transforming parasite Theileria annulata. mBio, 15(6), e0341223. American Society for Microbiology 10.1128/mbio.03412-23

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Theileria annulata is a tick-transmitted apicomplexan parasite that gained the unique ability among parasitic eukaryotes to transform its host cell, inducing a fatal cancer-like disease in cattle. Understanding the mechanistic interplay between the host cell and malignant Theileria species that drives this transformation requires the identification of responsible parasite effector proteins. In this study, we used TurboID-based proximity labeling, which unbiasedly identified secreted parasite proteins within host cell compartments. By fusing TurboID to nuclear export or localization signals, we biotinylated proteins in the vicinity of the ligase enzyme in the nucleus or cytoplasm of infected macrophages, followed by mass spectrometry analysis. Our approach revealed with high confidence nine nuclear and four cytosolic candidate parasite proteins within the host cell compartments, eight of which had no orthologs in non-transforming T. orientalis. Strikingly, all eight of these proteins are predicted to be highly intrinsically disordered proteins. We discovered a novel tandem arrayed protein family, nuclear intrinsically disordered proteins (NIDP) 1-4, featuring diverse functions predicted by conserved protein domains. Particularly, NIDP2 exhibited a biphasic host cell-cycle-dependent localization, interacting with the EB1/CD2AP/CLASP1 parasite membrane complex at the schizont surface and the tumor suppressor stromal antigen 2 (STAG2), a cohesion complex subunit, in the host nucleus. In addition to STAG2, numerous NIDP2-associated host nuclear proteins implicated in various cancers were identified, shedding light on the potential role of the T. annulata exported protein family NIDP in host cell transformation and cancer-related pathways.IMPORTANCETurboID proximity labeling was used to identify secreted proteins of Theileria annulata, an apicomplexan parasite responsible for a fatal, proliferative disorder in cattle that represents a significant socio-economic burden in North Africa, central Asia, and India. Our investigation has provided important insights into the unique host-parasite interaction, revealing secreted parasite proteins characterized by intrinsically disordered protein structures. Remarkably, these proteins are conspicuously absent in non-transforming Theileria species, strongly suggesting their central role in the transformative processes within host cells. Our study identified a novel tandem arrayed protein family, with nuclear intrinsically disordered protein 2 emerging as a central player interacting with established tumor genes. Significantly, this work represents the first unbiased screening for exported proteins in Theileria and contributes essential insights into the molecular intricacies behind the malignant transformation of immune cells.

Item Type:

Journal Article (Original Article)


05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Brühlmann, Francis, Perry, Carmen, Griessen, Charlotte, Gunasekera, Kapila, Reymond, Jean-Louis, Naguleswaran, Arunasalam, Rottenberg, Sven, Woods, Kerry, Olias, Philipp Alexander


600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry




American Society for Microbiology




Pubmed Import

Date Deposited:

16 May 2024 10:36

Last Modified:

13 Jun 2024 00:15

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Babesia BioID Cryptosporidium East Coast fever Plasmodium Toxoplasma cancer cattle malaria neglected tropical disease protozoa theileriosis





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