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A Novel C-Terminal Homologue of Aha1 Co-Chaperone Binds to Heat Shock Protein 90 and Stimulates Its ATPase Activity in Entamoeba histolytica

Singh, Meetali and Shah, Varun and Tatu, Utpal (2014) A Novel C-Terminal Homologue of Aha1 Co-Chaperone Binds to Heat Shock Protein 90 and Stimulates Its ATPase Activity in Entamoeba histolytica. In: JOURNAL OF MOLECULAR BIOLOGY, 426 (8). pp. 1786-1798.

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Official URL: http://dx.doi.org/10.1016/j.jmb.2014.01.008

Abstract

Cytosolic heat shock protein 90 (Hsp90) has been shown to be essential for many infectious pathogens and is considered a potential target for drug development. In this study, we have carried out biochemical characterization of Hsp90 from a poorly studied protozoan parasite of clinical importance, Entamoeba histolytica. We have shown that Entamoeba Hsp90 can bind to both ATP and its pharmacological inhibitor, 17-AAG (17-allylamino-17-demethoxygeldanamycin), with K-d values of 365.2 and 10.77 mu M, respectively, and it has a weak ATPase activity with a catalytic efficiency of 4.12 x 10(-4) min(-1) mu M-1. Using inhibitor 17-AAG, we have shown dependence of Entamoeba on Hsp90 for its growth and survival. Hsp90 function is regulated by various co-chaperones. Previous studies suggest a lack of several important co-chaperones in E. histolytica. In this study, we describe the presence of a novel homologue of co-chaperone Aha1 (activator of Hsp90 ATPase), EhAha1c, lacking a canonical Aha1 N-terminal domain. We also show that EhAha1c is capable of binding and stimulating ATPase activity of EhHsp90. In addition to highlighting the potential of Hsp90 inhibitors as drugs against amoebiasis, our study highlights the importance of E. histolytica in understanding the evolution of Hsp90 and its co-chaperone repertoire. (C) 2014 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Publication: JOURNAL OF MOLECULAR BIOLOGY
Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Additional Information: Copyright for this article belongs to the ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, ENGLAND
Keywords: Hsp90; 17-AAG; Entamoeba; co-chaperones; Aha1
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 19 May 2014 05:24
Last Modified: 19 May 2014 05:24
URI: http://eprints.iisc.ac.in/id/eprint/49094

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