| Full text | |
| Author(s): |
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.
Total Authors: 9
|
| Affiliation: | [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
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | Biochimie; v. 182, p. 51-60, MAR 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
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) | |
| FAPESP's process: | 14/25967-4 - Characterization of the role of ATPase domains and human co-chaperones Hsp40 and hop in cellular mechanisms of thermal tolerance and suppression of protein aggregation |
| Grantee: | Natália Galdi Quel |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| 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 Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/11496-3 - Role of TERRA in telomere regulation and replicative senescence in Leishmania major |
| Grantee: | Edna Gicela Ortiz Morea |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 18/04375-2 - Studies about the biogenesis and composition of the Leishmania spp. ribonucleoprotein complex and its regulation |
| Grantee: | Maria Isabel Nogueira Cano |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis |
| Grantee: | Carlos Henrique Inacio Ramos |
| Support Opportunities: | Research Projects - Thematic Grants |