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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.)

Structural, thermodynamic and functional studies of human 71 kDa heat shock cognate protein (HSPA8/hHsc70)

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Author(s):
Melo Silva, Noeli Soares [1] ; de Camargo Rodrigues, Luiz Fernando [2] ; Dores-Silva, Paulo Roberto [1, 3] ; Montanari, Carlos Alberto [1] ; Inacio Ramos, Carlos Henrique [4] ; Souza Barbosa, Leandro Ramos [2, 5] ; Borges, Julio Cesar [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Sao Carlos Inst Chem, Sao Carlos, SP - Brazil
[2] Univ Sao Paulo, Inst Phys, Sao Paulo, SP - Brazil
[3] Univ Calif San Diego, Dept Surg, Div Trauma Crit Care Burns & Acute Care Surg, Sch Med, La Jolla, CA 92093 - USA
[4] Univ Campinas UNICAMP, Inst Chem, Campinas, SP - Brazil
[5] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Synchrotron Light Lab LNLS, Campinas - Brazil
Total Affiliations: 5
Document type: Journal article
Source: BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS; v. 1869, n. 12 DEC 2021.
Web of Science Citations: 0
Abstract

Human 71 kDa heat shock cognate protein (HSPA8, also known as Hsc70, Hsp70-8, Hsc71, Hsp71 or Hsp73) is a constitutively expressed chaperone that is critical for cell proteostasis. In the cytosol, HSPA8 plays a pivotal role in folding and refolding, facilitates protein trafficking across membranes and targets proteins for degradation, among other functions. Here, we report an in solution study of recombinant HSPA8 (rHSPA8) using a variety of biophysical and biochemical approaches. rHSPA8 shares several structural and functional similarities with others human Hsp70s. It has two domains with different stabilities and interacts with adenosine nucleotides with dissociation constants in the low micromolar range, which were higher in the presence of Mg2+. rHSPA8 showed lower ATPase activity than its homolog HSPA5/hGrp78/hBiP, but it was 4-fold greater than that of recombinant HSPA1A/hHsp70-1A, with which it is 86% identical. Small angle X-ray scattering indicated that rHSPA8 behaved as an elongated monomeric protein in solution with dimensions similar to those observed for HSPA1A. In addition, rHSPA8 showed structural flexibility between its compacted and extended conformations. The data also indicated that HSPA8 has capacity in preventing the aggregation of model client proteins. The present study expands the understanding of the structure and activity of this chaperone and aligns with the idea that human homologous Hsp70s have divergent functions. (AU)

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: 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: 17/26131-5 - 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: 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
FAPESP's process: 15/15822-1 - Physicochemical and structural properties of Ionic Liquids and drugs interacting with biologicaly relevant systems.
Grantee:Leandro Ramos Souza Barbosa
Support type: Regular Research Grants
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: 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 type: Scholarships in Brazil - Post-Doctorate