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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Low resolution structural characterization of the Hsp70-interacting protein - Hip - from Leishmania braziliensis emphasizes its high asymmetry

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Author(s):
Dores-Silva, P. R. [1] ; Silva, E. R. [1] ; Gomes, F. E. R. [1] ; Silva, K. P. [1] ; Barbosa, L. R. S. [2] ; Borges, J. C. [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Inst Quim Sao Carlos, Grp Biol Mol & Bioquim, BR-13560970 Sao Carlos, SP - Brazil
[2] Univ Sao Paulo, Grp Biofis, Dept Fis Geral, Inst Fis, BR-05508090 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Archives of Biochemistry and Biophysics; v. 520, n. 2, p. 88-98, APR 15 2012.
Web of Science Citations: 7
Abstract

The Hsp70 is an essential molecular chaperone in protein metabolism since it acts as a pivot with other molecular chaperone families. Several co-chaperones act as regulators of the Hsp70 action cycle, as for instance Hip (Hsp70-interacting protein). Hip is a tetratricopeptide repeat protein (TPR) that interacts with the ATPase domain in the Hsp70-ADP state, stabilizing it and preventing substrate dissociation. Molecular chaperones from protozoans, which can cause some neglected diseases, are poorly studied in terms of structure and function. Here, we investigated the structural features of Hip from the protozoa Leishmania braziliensis (LbHip), one of the causative agents of the leishmaniasis disease. LbHip was heterologously expressed and purified in the folded state, as attested by circular dichroism and intrinsic fluorescence emission techniques. LbHip forms an elongated dimer, as observed by analytical gel filtration chromatography, analytical ultracentrifugation and small angle X-ray scattering (SAXS). With the SAXS data a low resolution model was reconstructed, which shed light on the structure of this protein, emphasizing its elongated shape and suggesting its domain organization. We also investigated the chemical-induced unfolding behavior of LbHip and two transitions were observed. The first transition was related to the unfolding of the TPR domain of each protomer and the second transition of the dimer dissociation. Altogether. LbHip presents a similar structure to mammalian Hip, despite their low level of conservation, suggesting that this class of eukaryotic protein may use a similar mechanism of action. (C) 2012 Elsevier Inc. All rights reserved. (AU)