Insights into the structure and function of the C-terminus of SGTs (small glutamine-rich TPR-containing proteins): A study of the Aedes aegypti homolog

Autor(es)

Quel, Natalia G. ^{[1, 2]} ; Rodrigues, Luiz Fernando de C. ^[3] ; Aragao, Annelize Z. B. ^[1] ; Pinheiro, Glaucia M. S. ^[1] ; Camacho, Rafael P. ^[1] ; Souto, Denio E. P. ^[4] ; Kubota, Lauro T. ^{[1, 5]} ; Barbosa, Leandro R. S. ^{[3, 6]} ; Ramos, Carlos H. I. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil

^[2] Natl Inst Sci Technol Struct Biol & Bioimage INCT, Sao Carlos - Brazil

^[3] Univ Sao Paulo, Inst Phys, BR-05508090 Sao Paulo, SP - Brazil

^[4] Fed Univ Paran UFPR, Dept Chem, BR-81530900 Curitiba, PR - Brazil

^[5] Natl Inst Sci & Technol Bioanalyt INCTBio, Campinas - Brazil

^[6] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Synchrotron Light Lab LNLS, Campinas - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Biochimie; v. 187, p. 131-143, AUG 2021.
• Citações Web of Science: 0

Resumo

SGTs (small glutamine-rich TPR-containing proteins) are dimeric proteins that belong to the class of co-chaperones characterized by the presence of TPR domains (containing tetratricopeptide repeats). Human (SGTA) and yeast (Sgt2) SGTs are characterized by three distinct domains: an N-terminal dimerization domain, a central TPR-domain important for binding to other proteins (chaperones included) and a C-terminal domain involved in hydrophobic interactions. Both these SGTs are involved in the cellular PQC (protein quality control) system, as they interact with chaperones and have functions that aid stress recovery. However, there are differences between them, such as structural features and binding specificities, that could be better understood if other orthologous proteins were studied. Therefore, we produced and characterized a putative SGT protein, designated AaSGT, from the mosquito Aedes aegypti, which is a vector of several diseases, such as dengue and Zika. The protein was produced as a folded dimer which was stable up to 40 degrees C and was capable of binding to AaHsp90 and fully protecting a model protein, alpha-synuclein, from aggregation. The conformation of AaSGT was investigated by biophysical tools and small angle X-ray scattering, which showed that the protein had an elongated conformation and that its C-terminal domain was mainly disordered. The results with a C-terminal deletion mutant supported these observations. Altogether, these results are consistent with those from other functional SGT proteins and add to the understanding of the PQC system in Aedes aegypti, an important aim that may help to develop inhibitory strategies against this vector of neglected diseases. (C) 2021 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU)

• Processo FAPESP: 16/05019-0 - A influência termodinâmica e estrutural de líquidos iônicos em sistemas biomiméticos de membrana
• Beneficiário: Natália Fernandes de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 12/01953-9 - Proteínas em condição de fibrilação: caracterização estrutural e espectroscópica em função de agentes desnaturantes
• Beneficiário: Leandro Ramos Souza Barbosa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/25967-4 - Caracterização do papel de domínios ATPase e das co-chaperonas Hsp40 e hop humanas nos mecanismos celulares de termotolerância e supressão de agregação proteica
• Beneficiário: Natália Galdi Quel
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/26131-5 - Chaperoma: estudo da relação entre a estrutura dos seus componentes e a manutenção da proteostase
• Beneficiário: Carlos Henrique Inacio Ramos
• Modalidade de apoio: 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
• Modalidade de apoio: Auxílio à Pesquisa - Regular