Molecular Chaperones Involved in Protein Recovery from Aggregates are Present in Protozoa Causative of Malaria and Leishmaniasis

Author(s)

Batista, Fernanda A. H. ^{[1, 2]} ; Dores-Silva, Paulo R. ^[2] ; Borges, Julio C. ^[2]

Affiliation

^[1] CNPEM, Lab Nacl Biociencias LNBio, BR-13083970 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Inst Quim Sao Carlos, POB 780, BR-13560970 Sao Carlos, SP - Brazil

• Document type: Review article
• Source: CURRENT PROTEOMICS; v. 16, n. 1, p. 12-21, 2019.
• Web of Science Citations: 0

Abstract

Molecular chaperones have several critical functions in protein metabolism. Among them, some are involved in processes that culminate in the extraction of entangled polypeptides from protein aggregates, releasing unfolded structures prone to be refolded or directed to degradation. This action avoids the effect of toxic aggregates on cells and tissues. Molecular chaperones belonging to the Hsp100 family are widely distributed from unicellular and sessile organisms up to fungi and plants, exerting key functions related to the reduction of the effects caused by different forms of stress. The Hsp100 proteins belong to the AAA+ (ATPases Associated with diverse cellular Activities) family and form multichaperone systems with Hsp70 and small Hsp chaperones families. However, Hsp100 are absent in metazoan, where protein disaggregation action is performed by a system involving the Hsp70 family, including Hsp110 and J-protein co-chaperones. Here, the structural and functional aspects of these protein disaggregation systems will be reviewed and discussed in the perspective of the Hsp100 system absent in the metazoan kingdom. This feature focuses on Hsp100 as a hot spot for drug discovery against human infectious diseases such as leishmaniasis and malaria, as Hsp100 is critical for microorganisms. The current data available for Hsp100 in Leishmania spp. and Plasmodium spp. are also reviewed. (AU)

• FAPESP's process: 14/07206-6 - Studies of the mitochondrial HSP70 of human and protozoa: structural and functional approaches
• Grantee: Julio Cesar Borges
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/16646-0 - Human mortalin: interaction with co-chaperones, p53 and mutants, aggregation kinectics, regulation/modulation and vesicle secretion
• Grantee: Paulo Roberto das Dores da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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: 11/23110-0 - Using isothermal titration calorimetry for the determination of thermodynamic properties of protein-ligand and protein-protein interactions
• Grantee: Julio Cesar Borges
• Support Opportunities: Regular Research Grants