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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.)

Revealing the interaction mode of the highly flexible Sorghum bicolor Hsp70/Hsp90 organizing protein (Hop): A conserved carboxylate clamp confers high affinity binding to Hsp90

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Adao, Regina [1, 2] ; Zanphorlin, Leticia M. [1, 3] ; Lima, Tatiani B. [1] ; Sriranganadane, Dev [1] ; Dahlstrom, Kathe M. [1] ; Pinheiro, Glaucia M. S. [1] ; Gozzo, Fabio C. [1] ; Barbosa, Leandro R. S. [4] ; Ramos, Carlos H. I. [1]
Total Authors: 9
[1] Univ Estadual Campinas, Inst Chem, UNICAMP, POB 6154, BR-13083970 Campinas, SP - Brazil
[2] Fed Univ ABC UFABC, Ctr Nat & Human Sci CCNH, Santo Andre, SP - Brazil
[3] Brazilian Bioethanol Sci & Technol Lab CTBE, Natl Ctr Res Energy & Mat, Campinas, SP - Brazil
[4] Univ Sao Paulo, Inst Phys, Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF PROTEOMICS; v. 191, n. SI, p. 191-201, JAN 16 2019.
Web of Science Citations: 0

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 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: 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