| Full text | |
| Author(s): |
Adao, Regina
;
Zanphorlin, Leticia M.
;
Lima, Tatiani B.
;
Sriranganadane, Dev
;
Dahlstrom, Kathe M.
;
Pinheiro, Glaucia M. S.
;
Gozzo, Fabio C.
;
Barbosa, Leandro R. S.
;
Ramos, Carlos H. I.
Total Authors: 9
|
| Document type: | Journal article |
| Source: | JOURNAL OF PROTEOMICS; v. 191, p. 11-pg., 2019-01-16. |
| Abstract | |
Proteostasis is dependent on the Hsp70/Hsp90 system (the two chaperones and their co-chaperones). Of these, Hop (Hsp70/Hsp90 organizing protein), also known as Sti1, forms an important scaffold to simultaneously binding to both Hsp70 and Hsp90. Hop/Sti1 has been implicated in several disease states, for instance cancer and transmissible spongiform encephalopathies. Therefore, human and yeast homologous have been better studied and information on plant homologous is still limited, even though plants are continuously exposed to environmental stress. Particularly important is the study of crops that are relevant for agriculture, such as Sorghum bicolor, a C4 grass that is among the five most important cereals and is considered as a bioenergy feedstock. To increase the knowledge on plant chaperones, the hop putative gene for Sorghum bicolor was cloned and the biophysical and structural characterization of the protein was done by cross-linking coupled to mass spectroscopy, small angle X-ray scattering and structural modeling. Additionally, the binding to a peptide EEVD motif, which is present in both Hsp70 and Hsp90, was studied by isothermal titration calorimetry and hydrogen/deuterium exchange and the interaction pattern structurally modeled. The results indicate SbHop as a highly flexible, mainly alpha-helical monomer consisting of nine tetratricopeptide repeat domains, of which one confers high affinity binding to Hsp90 through a conserved carboxylate clamp. Moreover, the present insights into the conserved interactions formed between Hop and Hsp90 can help to design strategies for potential therapeutic approaches for the diseases in which Hop has been implicated. (AU) | |
| FAPESP's process: | 14/17264-3 - New frontiers in structural proteomics: characterizing protein and protein complex structures by mass spectrometry |
| Grantee: | Fabio Cesar Gozzo |
| Support Opportunities: | 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 Opportunities: | 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 Opportunities: | Regular Research Grants |