- Title
- Plasmodium falciparum Hsp70-x : a heat shock protein at the host-parasite interface
- Creator
- Hatherley, Rowan
- Creator
- Blatch, Gregory L
- Creator
- Tastan Bishop, Özlem
- Date Issued
- 2013
- Date
- 2013
- Type
- Article
- Identifier
- vital:6489
- Identifier
- http://hdl.handle.net/10962/d1007081
- Identifier
- https://dx.doi.org/10.1080/07391102.2013.834849
- Description
- Plasmodium falciparum 70 kDa heat shock proteins (PfHsp70s) are expressed at all stages of the pathogenic erythrocytic phase of the malaria parasite lifecycle. There are six PfHsp70s,all of which have orthologues in other plasmodial species, except for PfHsp70-x which is unique to P. falciparum. This paper highlights a number of original results obtained by a detailed bioinformatics analysis of the protein. Large scale sequence analysis indicated the presence of an extended transit peptide sequence of PfHsp70-x which potentially directs it to the endoplasmic reticulum (ER). Further analysis showed that PfHsp70-x does not have an ER-retention sequence, suggesting that the protein transits through the ER and is secreted into the parasitophorous vacuole (PV) or beyond into the erythrocyte cytosol. These results are consistent with experimental findings. Next, possible interactions between PfHsp70-x and exported P. falciparum Hsp40s or host erythrocyte DnaJs were interrogated by modeling and docking. Docking results indicated that interaction between PfHsp70-x and each of the Hsp40s, regardless of biological feasibility, seems equally likely. This suggests that J domain might not provide the specificity in the formation of unique Hsp70-Hsp40 complexes, but that the specificity might be provided by other domains of Hsp40s. By studying different structural conformations of PfHsp70-x, it was shown that Hsp40s can only bind when PfHsp70-x is in a certain conformation. Additionally, this work highlighted the possible dependence of the substrate binding domain residues on the orientation of the α-helical lid for formation of the substrate binding pocket.
- Format
- 91 pages
- Format
- Language
- English
- Relation
- Hatherley, R., Blatch, G.L.,Tastan Bishop, OPlasmodium falciparum Hsp70-x: A Heat Shock Protein at the Host - Parasite Interface (2013). Journal of biomolecular structure & dynamics. Available at; 10.1080/07391102.2013.834849 ; http://arxiv.org/abs/1307.3446
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Tastan Bishop, Ozlem (Prof)
RU Department of Biochemistry, Microbiology and Bioinformatics
SDG 03. Good Health and Well-Being
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