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A Plasmodium falciparum FK506-binding protein (FKBP) with peptidyl-prolyl cis-trans isomerase and chaperone activities.
Mol Biochem Parasitol. 2005 Feb; 139(2):185-95.MB

Abstract

The immunosuppressive drugs FK506 and rapamycin have anti-malarial properties but their mechanisms of action against malaria parasites remain unknown. The pathway by which these drugs cause immunosuppression in humans is known to involve an FK506-binding protein (FKBP). Homologues of FKBPs have been identified in almost every organism in which they have been sought. Here, we describe the characterisation of the first member of the FKBP family identified in the human malarial parasite, Plasmodium falciparum. This 35-kDa protein, PfFKBP35, comprises a single, N-terminal, FKBP domain and a C-terminal tripartite tetratricopeptide repeat domain. A recombinant form of PfFKBP35, like most other FKBPs, displayed peptidyl-prolyl cis-trans isomerase activity that was inhibitable by FK506 and rapamycin. Unusually the phosphatase activity of calcineurin, the target of the FK506-FKBP complex in T-lymphocytes, was inhibited by PfFKBP35 independently of FK506 binding. PfFKBP35 also inhibited the thermal aggregation in vitro of two model substrates, suggesting that it has general chaperone properties. Analysis of the P. falciparum genome database suggested this to be the only FKBP present in the parasite. The function of this protein remains unknown but the presence of tetratricopeptide repeat motifs suggests a role in intracellular protein transport or modulation of protein function.

Authors+Show Affiliations

Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15664653

Citation

Monaghan, Paul, and Angus Bell. "A Plasmodium Falciparum FK506-binding Protein (FKBP) With Peptidyl-prolyl Cis-trans Isomerase and Chaperone Activities." Molecular and Biochemical Parasitology, vol. 139, no. 2, 2005, pp. 185-95.
Monaghan P, Bell A. A Plasmodium falciparum FK506-binding protein (FKBP) with peptidyl-prolyl cis-trans isomerase and chaperone activities. Mol Biochem Parasitol. 2005;139(2):185-95.
Monaghan, P., & Bell, A. (2005). A Plasmodium falciparum FK506-binding protein (FKBP) with peptidyl-prolyl cis-trans isomerase and chaperone activities. Molecular and Biochemical Parasitology, 139(2), 185-95.
Monaghan P, Bell A. A Plasmodium Falciparum FK506-binding Protein (FKBP) With Peptidyl-prolyl Cis-trans Isomerase and Chaperone Activities. Mol Biochem Parasitol. 2005;139(2):185-95. PubMed PMID: 15664653.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Plasmodium falciparum FK506-binding protein (FKBP) with peptidyl-prolyl cis-trans isomerase and chaperone activities. AU - Monaghan,Paul, AU - Bell,Angus, PY - 2004/10/27/revised PY - 2004/10/30/accepted PY - 2005/1/25/pubmed PY - 2005/4/22/medline PY - 2005/1/25/entrez SP - 185 EP - 95 JF - Molecular and biochemical parasitology JO - Mol Biochem Parasitol VL - 139 IS - 2 N2 - The immunosuppressive drugs FK506 and rapamycin have anti-malarial properties but their mechanisms of action against malaria parasites remain unknown. The pathway by which these drugs cause immunosuppression in humans is known to involve an FK506-binding protein (FKBP). Homologues of FKBPs have been identified in almost every organism in which they have been sought. Here, we describe the characterisation of the first member of the FKBP family identified in the human malarial parasite, Plasmodium falciparum. This 35-kDa protein, PfFKBP35, comprises a single, N-terminal, FKBP domain and a C-terminal tripartite tetratricopeptide repeat domain. A recombinant form of PfFKBP35, like most other FKBPs, displayed peptidyl-prolyl cis-trans isomerase activity that was inhibitable by FK506 and rapamycin. Unusually the phosphatase activity of calcineurin, the target of the FK506-FKBP complex in T-lymphocytes, was inhibited by PfFKBP35 independently of FK506 binding. PfFKBP35 also inhibited the thermal aggregation in vitro of two model substrates, suggesting that it has general chaperone properties. Analysis of the P. falciparum genome database suggested this to be the only FKBP present in the parasite. The function of this protein remains unknown but the presence of tetratricopeptide repeat motifs suggests a role in intracellular protein transport or modulation of protein function. SN - 0166-6851 UR - https://www.unboundmedicine.com/medline/citation/15664653/A_Plasmodium_falciparum_FK506_binding_protein__FKBP__with_peptidyl_prolyl_cis_trans_isomerase_and_chaperone_activities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-6851(04)00309-3 DB - PRIME DP - Unbound Medicine ER -