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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Identification of two p23 co-chaperone isoforms in Leishmania braziliensis exhibiting similar structures and Hsp90 interaction properties despite divergent stabilities

Texto completo
Autor(es):
Batista, Fernanda A. H. [1] ; Almeida, Glessler S. [2] ; Seraphim, Thiago V. [1] ; Silva, Kelly P. [1] ; Murta, Silvane M. F. [3] ; Barbosa, Leandro R. S. [4] ; Borges, J. Ulio C. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil
[2] Univ Fed Sao Carlos, Dept Genet & Evolucao, Programa Posgrad Genet Evolut & Biol Mol, BR-13560 Sao Carlos, SP - Brazil
[3] Fiocruz MS, Ctr Pesquisa Rene Rachou, Belo Horizonte, MG - Brazil
[4] Univ Sao Paulo, Inst Fis, BR-01498 Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: FEBS Journal; v. 282, n. 2, p. 388-406, JAN 2015.
Citações Web of Science: 11
Resumo

The small acidic protein called p23 acts as a co-chaperone for heat-shock protein of 90 kDa (Hsp90) during its ATPase cycle. p23 proteins inhibit Hsp90 ATPase activity and show intrinsic chaperone activity. A search for p23 in protozoa, especially trypanosomatids, led us to identify two putative proteins in the Leishmania braziliensis genome that share approximately 30% identity with each other and with the human p23. To understand the presence of two p23 isoforms in trypanosomatids, we obtained the recombinant p23 proteins of L. braziliensis (named Lbp23A and Lbp23B) and performed structural and functional studies. The recombinant proteins share similar solution structures; however, temperature-and chemicalinduced unfolding experiments showed that Lbp23A is more stable than Lbp23B, suggesting that they may have different functions. Lbp23B prevented the temperature-induced aggregation of malic dehydrogenase more efficiently than did Lbp23A, whereas the two proteins had equivalent efficiencies with respect to preventing the temperature-induced aggregation of luciferase. Both proteins interacted with L. braziliensis Hsp90 (LbHsp90) and inhibited its ATPase activity, although their efficiencies differed. In vivo identification studies suggested that both proteins are present in L. braziliensis cells grown under different conditions, although Lbp23B may undergo post-translation modifications. Interaction studies indicated that both Lbp23 proteins interact with LbHsp90. Taken together, our data suggest that the two protozoa p23 isoforms act similarly when regulating Hsp90 function. However, they also have some differences, indicating that the L. braziliensis Hsp90 machine has features providing an opportunity for novel forms of selective inhibition of protozoan Hsp90. (AU)

Processo FAPESP: 07/05001-4 - Estudos dos sistemas chaperones moleculares HSP70 e HSP90 de parasitas
Beneficiário:Julio Cesar Borges
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 12/50161-8 - Estudo da estrutura e função da chaperona Hsp90 com ênfase no seu papel em homeostase celular
Beneficiário:Carlos Henrique Inacio Ramos
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 11/23110-0 - Uso da calorimetria de titulação isotérmica para a determinação de propriedades termodinâmicas de interação de proteína-ligante e proteína-proteína
Beneficiário:Julio Cesar Borges
Linha de fomento: Auxílio à Pesquisa - Regular