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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 sequence identity but high structural and functional conservation: The case of Hsp70/Hsp90 organizing protein (Hop/Sti1) of Leishmania braziliensis

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Author(s):
Batista, Fernanda A. H. [1] ; Seraphim, Thiago V. [1] ; Santos, Clelton A. [2] ; Gonzaga, Marisvanda R. [1] ; Barbosa, Leandro R. S. [3] ; Ramos, Carlos H. I. [2, 4] ; Borges, Julio C. [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Quim Sao Carlos, Av Trabalhador Saocarlense, 400 CP 780, BR-13560970 Sao Carlos, SP - Brazil
[2] Univ Estadual Campinas UNICAMP, Inst Quim, Rua Jose de Castro S-N, Cidade Univ, CP 6154, BR-13083970 Campinas, SP - Brazil
[3] Univ Sao Paulo, Inst Fis, Av Prof Lineu Prestes, 748, CP 26077, Sao Paulo, SP - Brazil
[4] Inst Nacl Ciencia & Tecnol Biol Estrutural & Bioi, Av Brigadeiro Trompowsky S-N, Cidade Univ, Rio De Janeiro, RJ - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Archives of Biochemistry and Biophysics; v. 600, p. 12-22, JUN 15 2016.
Web of Science Citations: 3
Abstract

Parasites belonging to the genus Leishmania are subjected to extensive environmental changes during their life cycle; molecular chaperones/co-chaperones act as protagonists in this scenario to maintain cellular homeostasis. Hop/Sti1 is a co-chaperone that connects the Hsp90 and Hsp70 systems, modulating their ATPase activities and affecting the fate of client proteins because it facilitates their transfer from the Hsp70 to the Hsp90 chaperone. Hop/Sti1 is one of the most prevalent co-chaperones, highlighting its importance despite the relatively low sequence identity among orthologue proteins. This multi-domain protein comprises three tetratricopeptides domains (TPR1, TPR2A and TPR2B) and two Asp/Pro-rich domains. Given the importance of Hop/Sti1 for the chaperone system and for Leishmania protozoa viability, the Leishmania braziliensis Hop (LbHop) and a truncated mutant (LbHop(TPR2AB)) were characterized. Structurally, both proteins are alpha-helix-rich and highly elongated monomeric proteins. Functionally, they inhibited the ATPase activity of Leishmania braziliensis Hsp90 (LbHsp90) to a similar extent, and the thermodynamic parameters of their interactions with LbHsp90 were similar, indicating that TPR2A-TPR2B forms the functional center for the LbHop interaction with LbHsp90. These results highlight the structural and functional similarity of Hop/Sti1 proteins, despite their low sequence conservation compared to the Hsp70 and Hsp90 systems, which are phylogenetic highly conserved. (C) 2016 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 14/07206-6 - Studies of the mitochondrial HSP70 of human and protozoa: structural and functional approaches
Grantee:Julio Cesar Borges
Support type: Regular Research Grants
FAPESP's process: 12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis
Grantee:Carlos Henrique Inacio Ramos
Support type: Research Projects - Thematic Grants
FAPESP's process: 11/23110-0 - Using isothermal titration calorimetry for the determination of thermodynamic properties of protein-ligand and protein-protein interactions
Grantee:Julio Cesar Borges
Support type: Regular Research Grants