Plasmodium falciparum Hop: detailed analysis on complex formation with Hsp70 and Hsp90

Hatherley, Rowan; Clitheroe, Crystal-Leigh; Faya, Ngonidzashe; Tastan Bishop, Özlem

Title: Plasmodium falciparum Hop: detailed analysis on complex formation with Hsp70 and Hsp90
Creator: Hatherley, Rowan
Creator: Clitheroe, Crystal-Leigh
Creator: Faya, Ngonidzashe
Creator: Tastan Bishop, Özlem
Date Issued: 2015
Date: 2015
Type: text
Type: article
Identifier: http://hdl.handle.net/10962/125708
Identifier: vital:35810
Identifier: https://doi.10.1016/j.bbrc.2014.11.103
Description: The heat shock organizing protein (Hop) is important in modulating the activity and co-interaction of two chaperones: heat shock protein 70 and 90 (Hsp70 and Hsp90). Recent research suggested that Plasmodium falciparum Hop (PfHop), PfHsp70 and PfHsp90 form a complex in the trophozoite infective stage. However, there has been little computational research on the malarial Hop protein in complex with other malarial Hsps. Using in silico characterization of the protein, this work showed that individual domains of Hop are evolving at different rates within the protein. Differences between human Hop (HsHop) and PfHop were identified by motif analysis. Homology modeling of PfHop and HsHop in complex with their own cytosolic Hsp90 and Hsp70 C-terminal peptide partners indicated excellent conservation of the Hop concave TPR sites bound to the C-terminal motifs of partner proteins. Further, we analyzed additional binding sites between Hop and Hsp90, and showed, for the first time, that they are distinctly less conserved between human and malaria parasite. These sites are located on the convex surface of Hop TPR2, and involved in interactions with the Hsp90 middle domain. Since the convex sites are less conserved than the concave sites, it makes their potential for malarial inhibitor design extremely attractive (as opposed to the concave sites which have been the focus of previous efforts).
Format: 6 pages
Format: pdf
Language: English
Relation: Biochemical and biophysical research communications
Relation: Hatherley, R., Clitheroe, C.L., Faya, N. and Bishop, Ö.T., 2015. Plasmodium falciparum Hop: detailed analysis on complex formation with Hsp70 and Hsp90. Biochemical and biophysical research communications, 456(1), pp.440-445
Relation: Biochemical and biophysical research communications volume 456 number 1 440 445 2015 0006-291X
Rights: Biochemical and biophysical research communications
Rights: Use of this resource is governed by the terms and conditions of the Elsevier Terms & Conditions statement (https://www.elsevier.com/legal/elsevier-website-terms-and-conditions)

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Tastan Bishop, Ozlem (Prof)

RU Research Unit in Bioinformatics (RUBi)

RU Department of Biochemistry, Microbiology and Biotechnology

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