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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Solution structure of Plasmodium falciparum Hsp90 indicates a high flexible dimer

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Author(s):
Silva, Noeli S. M. [1] ; Torricillas, Marcela S. [1] ; Minari, Karine [1, 2] ; Barbosa, Leandro R. S. [3] ; Seraphim, V, Thiago ; Borges, Julio C. [4]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Sao Carlos Inst Chem, Sao Carlos, SP - Brazil
[2] Univ Fed Sao Carlos, Ctr Biol & Hlth Sci, BR-13560970 Sao Carlos, SP - Brazil
[3] Univ Sao Paulo, Inst Phys, Sao Paulo, SP - Brazil
[4] Seraphim, Thiago, V, Univ Sao Paulo, Sao Carlos Inst Chem, Sao Carlos, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Archives of Biochemistry and Biophysics; v. 690, SEP 15 2020.
Web of Science Citations: 0
Abstract

Hsp90 is a ubiquitous, homodimer and modular molecular chaperone. Each Hsp90 protomer has three different domains, named the N-terminal domain (NTD), middle domain (MD) and C-terminal domain (CTD). The Hsp90 molecular cycle involves ATP binding and hydrolysis, which drive conformational changes. Hsp90 is critical for the viability of eukaryotic organisms, including the protozoan that causes the severe form of malaria, Plasmodium falciparum, the growth and differentiation of which are compromised when Hsp90 is inhibited. Here, we characterize the structure of a recombinant P. falciparum Hsp90 (PfHsp90) protein, as well as its MD (PfHsp90MD) and NTD plus MD (PfHsp90NMD) constructs. All the proteins were obtained with high purity and in the folded state. PfHsp90 and PfHsp90NMD interacted with adenosine nucleotides via the NTD, and Mg2+ was critical for strong binding. PfHsp90 behaved mostly as elongated and flexible dimers in solution, which dissociate with a sub-micromolar dissociation constant. The PfHsp90MD and PfHsp90NMD constructs behaved as globular and elongated monomers, respectively, confirming the importance of the CTD for dimerization. Small angle X-ray scattering data were obtained for all the constructs, and ab initio models were constructed, revealing PfHsp90 in an open conformation and as a greatly elongated and flexible protein. (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 type: Regular Research 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 type: 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 type: Regular Research Grants
FAPESP's process: 17/07335-9 - Studies of human HSP70 isoforms residing in the cytoplasm and mitochondria and their high molecular weight oligomers: interaction with co-chaperones and client proteins
Grantee:Julio Cesar Borges
Support type: Regular Research Grants
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 type: Research Projects - Thematic Grants