Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/33562
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
Authors: Seraphim, Thiago Vargas
Alves, Marina De Matteu
Silva, Indjara Mallmann da
Gomes, Francisco Edvan Rodrigues
Silva, Kelly Pereira da
Murta, Silvane Maria Fonseca
Barbosa, Leandro Ramos Souza
Borges, Júlio Cesar
Affilliation: Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil.
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.
Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil.
Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil.
Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil.
Universidade de São Paulo. Instituto de Física. Departamento de Física Geral. São Paulo, SP, Brasil.
Universidade de São Paulo. Instituto de Química de São Carlos. São Carlos, SP, Brasil.
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.
Keywords: Plasmodium Falciparum
Leishmania braziliensis
keywords: Homeostase celular
Plasmodium Falciparum
Issue Date: 2013
Publisher: Public Library of Science
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.
DOI: 10.1371/journal.pone.0066822
ISSN: 1932-6203
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

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