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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

Grant number: 14/25967-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): September 13, 2019
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Carlos Henrique Inacio Ramos
Grantee:Natália Galdi Quel
Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


A number of human diseases known as 'conformational' is related to the incorrect protein folding. Misfolded proteins do not function correctly and may also form aggregates or amyloids, which are associated with hundreds of diseases including Alzheimer's and Parkinson's. Molecular chaperones and Hsps (heat shock proteins) participate in a cellular system known as PQC (Protein Quality Control) involved in maintaining protein homeostasis. There are specialized chaperones in aiding protein folding ('foldases'), in the inhibition of the aggregate formation ('holders') and in the resolubilisation of aggregates ('desagregases'). Interestingly, specialized desagregases have not yet been found in metazoan cell cytosol suggesting that other proteins may be involved with this function. Our group has extensive background in the study of protein folding and aggregation of proteins and chaperones and in this project we seek detailed information about the cellular mechanisms of protection against thermal stress and protein aggregation. Therefore, we will use yeast as a model to test thermotolerance and aggregation of prions and amyloid. First, a chimera of the ATPase domain of a human protein involved in neuronal diseases and suggested as a chaperone role, and Hsp104, yeast desagregase, will be produced and studied. We will also study the role of human co-chaperones Hsp40 and Hop in the suppression of protein aggregation since their yeast counterparts have this role. Another objective which depends on the results of the above objectives is the investigation of whether these proteins interact to form a protein complex that participates in the PQC system. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ABRAHAO, JOSIELLE; AMARO, BARBARA T.; PERES, BARBARA R.; QUEL, NATALIA G.; ARAGA, ANNELIZE Z. B.; MOREA, EDNA G. O.; CANO, MARIA ISABEL N.; HOURY, WALID A.; RAMOS, CARLOS H. I. Leishmania major RUVBL1 has a hexameric conformation in solution and, in the presence of RUVBL2, forms a heterodimer with ATPase activity. Archives of Biochemistry and Biophysics, v. 703, MAY 30 2021. Web of Science Citations: 0.
ARAUJO, SARA A.; MARTINS, GUSTAVO H.; QUEL, NATALIA G.; ARAGAO, ANNELIZE Z. B.; MOREA, EDNA G. O.; BORGES, JULIO C.; HOURY, WALID A.; CANO, MARIA I. N.; RAMOS, I, CARLOS H. Purification and characterization of a novel and conserved TPR-domain protein that binds both Hsp90 and Hsp70 and is expressed in all developmental stages of Leishmania major. Biochimie, v. 182, p. 51-60, MAR 2021. Web of Science Citations: 0.
QUEL, NATALIA G.; PINHEIRO, GLAUCIA M. S.; RODRIGUES, LUIZ FERNANDO DE C.; BARBOSA, LEANDRO R. S.; HOURY, WALID A.; RAMOS, I, CARLOS H. Heat shock protein 90 kDa (Hsp90) from Aedes aegypti has an open conformation and is expressed under heat stress. International Journal of Biological Macromolecules, v. 156, p. 522-530, AUG 1 2020. Web of Science Citations: 0.

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