Author | Seraphim, Thiago Vargas | |
Author | Alves, Marina De Matteu | |
Author | Silva, Indjara Mallmann da | |
Author | Gomes, Francisco Edvan Rodrigues | |
Author | Silva, Kelly Pereira da | |
Author | Murta, Silvane Maria Fonseca | |
Author | Barbosa, Leandro Ramos Souza | |
Author | Borges, Júlio Cesar | |
Access date | 2019-06-18T17:35:54Z | |
Available date | 2019-06-18T17:35:54Z | |
Document date | 2013 | |
Citation | SERAPHIM, Thiago Vargas et al. Low Resolution Structural Studies Indicate that the Activator of Hsp90 ATPase 1 (Aha1) of Leishmania braziliensis Has an Elongated Shape Which Allows Its Interaction with Both N- and M-Domains of Hsp90. PLoS One; v. 8, n. 6, p. 1-14, 2013. | pt_BR |
ISSN | 1932-6203 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/33562 | |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Homeostase celular | pt_BR |
Subject in Portuguese | Plasmodium Falciparum | pt_BR |
Title | Low Resolution Structural Studies Indicate that the Activator of Hsp90 ATPase 1 (Aha1) of Leishmania braziliensis Has an Elongated Shape Which Allows Its Interaction with Both N- and M-Domains of Hsp90 | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.pone.0066822 | |
Abstract | The Hsp90 molecular chaperone is essential for protein homeostasis and in the maturation of proteins involved with cell-cycle control. The low ATPase activity of Hsp90 is critical to drive its functional cycle, which is dependent on the Hsp90 cochaperones. The Activator of Hsp90 ATPase-1 (Aha1) is a protein formed by two domains, N- and C-terminal, that stimulates the Hsp90 ATPase activity by several folds. Although the relevance of Aha1 for Hsp90 functions has been proved, as well as its involvement in the desensitization to inhibitors of the Hsp90, the knowledge on its overall structure and behavior in solution is limited. In this work we present the functional and structural characterization of Leishmania braziliensis Aha1 (LbAha1). This protozoan is the causative agent of cutaneous and mucocutaneous leishmaniasis, a neglected disease. The recombinant LbAha1 behaves as an elongated monomer and is organized into two folded domains interconnected by a flexible linker. Functional experiments showed that LbAha1 interacts with L. braziliensis Hsp90 (LbHsp90) with micromolar dissociation constant in a stoichiometry of 2 LbAha1 to 1 LbHsp90 dimer and stimulates 10-fold the LbHsp90 ATPase activity showing positive cooperativity. Furthermore, the LbHsp90. | pt_BR |
Affilliation | Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil / Universidade Federal de São Carlos. Centro de Ciências Biológicas e da Saúde. São Carlos, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Instituto de Física. Departamento de Física Geral. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil. | pt_BR |
Subject | Plasmodium Falciparum | pt_BR |
Subject | Leishmania braziliensis | pt_BR |