| Full text | |
| Author(s): Show less - |
Coto, Amanda Lais de Souza
;
Pereira, Arthur Alexandre
;
Oliveira, Sabrina Dorta
;
Moritz, Milene Nobrega de Oliveira
;
da Rocha, Arthur Moraes Franco
;
Dores-Silva, Paulo Roberto
;
da Silva, Noeli Soares Melo
;
Nogueira, Ana Rita de Araujo
;
Gava, Lisandra Marques
;
Seraphim, Thiago Vagas
;
Borges, Julio Cesar
Total Authors: 11
|
| Document type: | Journal article |
| Source: | BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS; v. 1872, n. 1, p. 12-pg., 2023-10-26. |
| Abstract | |
J-domain proteins (JDPs) form a very large molecular chaperone family involved in proteostasis processes, such as protein folding, trafficking through membranes and degradation/disaggregation. JDPs are Hsp70 cochaperones capable of stimulating ATPase activity as well as selecting and presenting client proteins to Hsp70. In mitochondria, human DjC20/HscB (a type III JDP that possesses only the conserved J-domain in some region of the protein) is involved in [FeS] protein biogenesis and assists human mitochondrial Hsp70 (HSPA9). Human DjC20 possesses a zinc-finger domain in its N-terminus, which closely contacts the J-domain and appears to be essential for its function. Here, we investigated the hDjC20 structure in solution as well as the importance of Zn+2 for its stability. The recombinant hDjC20 was pure, folded and capable of stimulating HSPA9 ATPase activity. It behaved as a slightly elongated monomer, as attested by small-angle X-ray scattering and SEC-MALS. The presence of Zn2+ in the hDjC20 samples was verified, a stoichiometry of 1:1 was observed, and its removal by high concentrations of EDTA and DTPA was unfeasible. However, thermal and chemical denaturation in the presence of EDTA led to a reduction in protein stability, suggesting a synergistic action between the chelating agent and denaturators that facilitate protein unfolding depending on metal removal. These data suggest that the affinity of Zn+2 for the protein is very high, evidencing its importance for the hDjC20 structure. (AU) | |
| FAPESP's process: | 20/15947-7 - Mapping and mechanistic characterization of the interaction of the human HspA5 (BiP/Grp78/erHsp70) protein with the human Hep1 co-chaperone and with the Spike protein of the SARS-CoV-2 Coronavirus |
| Grantee: | Noeli Soares Melo da Silva |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| 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: | 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 |
| 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: | 21/02289-4 - Structural studies of the Activator of HSP90 ATPase (Aha) co-chaperone isoforms in Plasmodium falciparum in complex with the HSP90 chaperone and characterization of their cellular roles |
| Grantee: | Thiago Vargas Seraphim |
| 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: | 19/22422-0 - Cellular functional study of high molecular weight oligomers of mortaline and the effects of mitochondrial co-chaperones on their structure |
| Grantee: | Milene Nóbrega de Oliveira Moritz |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| 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 Opportunities: | Regular Research Grants |