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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

Texto completo
Autor(es):
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]
Número total de Autores: 9
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF PROTEOMICS; v. 191, n. SI, p. 191-201, JAN 16 2019.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 14/17264-3 - Novas fronteiras em proteômica estrutural: caracterizando estruturas de proteínas e complexos proteicos por espectrometria de massas
Beneficiário:Fabio Cesar Gozzo
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 15/15822-1 - Estudo das propriedades físico-químicas e estruturais de fármacos e líquidos iônicos com sistemas de relevância biológica
Beneficiário:Leandro Ramos Souza Barbosa
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/50161-8 - Estudo da estrutura e função da chaperona Hsp90 com ênfase no seu papel em homeostase celular
Beneficiário:Carlos Henrique Inacio Ramos
Linha de fomento: Auxílio à Pesquisa - Temático