| Texto completo | |
| Autor(es): |
Araujo, Sara A.
[1]
;
Martins, Gustavo H.
[1]
;
Quel, Natalia G.
[1, 2]
;
Aragao, Annelize Z. B.
[1]
;
Morea, Edna G. O.
[3]
;
Borges, Julio C.
[4, 2]
;
Houry, Walid A.
[5, 6]
;
Cano, Maria I. N.
[3]
;
Ramos, I, Carlos H.
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] I, Univ Campinas UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil
[2] I, Natl Inst Sci & Technol Struct Biol & Bioimage IN, Rio De Janeiro, RJ - Brazil
[3] Sao Paulo State Univ, Biosci Inst, Dept Chem & Biol Sci, BR-18618689 Botucatu, SP - Brazil
[4] Univ Sao Paulo, Sao Carlos Inst Chem, Sao Carlos, SP - Brazil
[5] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6 - Canada
[6] Univ Toronto, Dept Biochem, Toronto, ON M5G 1M1 - Canada
Número total de Afiliações: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Biochimie; v. 182, p. 51-60, MAR 2021. |
| Citações Web of Science: | 0 |
| Resumo | |
Heat shock proteins (Hsps) are involved in several important aspects of the cell proteostasis. Hsp90 interacts with at least a tenth of the cell proteome helping a large number of proteins to fold correctly. Hsp90 function is modulated by several co-chaperones having TPR (tetratricopeptide repeat) domains that allow for interaction with the C-terminal MEEVD motif of the chaperone. Another important chaperone, Hsp70, has a C-terminal EEVD motif that binds to TPR. Leishmania is a protozoan that causes leishmaniasis, a neglected disease in humans and other animals. There is still no effective treatment for leishmaniasis, however the study of structure and function of the proteins of the parasite may generate potential targets for future therapeutic intervention studies. In this work, the genome of Leishmania major was searched for a novel TPR-domain gene, which is conserved in Leishmania. The recombinant protein, LmTPR, was produced in pure and folded state and was characterized by biophysical tools as a monomer with an elongated conformation. Studies in Leishmania major were also preformed to complement these in vitro experiments. Splice Leader RNA-seq analysis and Western blot indicated that the protein was expressed in all developmental stages of the parasite. Binding assays confirmed that both Hsp90 and Hsp70 bind specifically to LmTPR. Finally, sequence and structural predictions indicated a C terminal region as a RPAP3 domain. Altogether, this study identified a novel TPR-domain co-chaperone of Hsp90 that is conserved and expressed in all developmental stages of Leishmania major. (C) 2021 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU) | |
| Processo FAPESP: | 14/25967-4 - Caracterização do papel de domínios ATPase e das co-chaperonas Hsp40 e hop humanas nos mecanismos celulares de termotolerância e supressão de agregação proteica |
| Beneficiário: | Natália Galdi Quel |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| 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 |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 19/11496-3 - PAPEL DO TERRA NA REGULAÇÃO DA MANUTENÇÃO DOS TELÔMEROS E NA SENESCÊNCIA REPLICATIVA EM Leishmania major |
| Beneficiário: | Edna Gicela Ortiz Morea |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 18/04375-2 - Estudos sobre a biogênese e composição do complexo ribonucleoprotéico da telomerase de Leishmania spp. e sua regulação |
| Beneficiário: | Maria Isabel Nogueira Cano |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 17/26131-5 - Chaperoma: estudo da relação entre a estrutura dos seus componentes e a manutenção da proteostase |
| Beneficiário: | Carlos Henrique Inacio Ramos |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |