Correct partner makes the difference: Septin G-interface plays a critical role in amyloid formation.

Autor: Kumagai PS; Instituto de Física de São Carlos, Universidade de São Paulo, Av. João Dagnone, 1100, São Carlos, SP CEP 13563-120, Brazil., Martins CS; Instituto de Física de São Carlos, Universidade de São Paulo, Av. João Dagnone, 1100, São Carlos, SP CEP 13563-120, Brazil., Sales EM; IPT-Institute for Technological Research, Av. Prof. Almeida Prado, 532, São Paulo, SP CEP 05508-280, Brazil; Instituto de Física, Universidade de São Paulo, Rua do Matão, 1371, São Paulo, SP CEP 05508-090, Brazil., Rosa HVD; Instituto de Física de São Carlos, Universidade de São Paulo, Av. João Dagnone, 1100, São Carlos, SP CEP 13563-120, Brazil., Mendonça DC; Instituto de Física de São Carlos, Universidade de São Paulo, Av. João Dagnone, 1100, São Carlos, SP CEP 13563-120, Brazil., Damalio JCP; Instituto Federal de Educação e Tecnologia de São Paulo, Campus Avaré, Av. Prof. Celso Ferreira da Silva, 1333, Avaré, SP CEP 18707-150, Brazil., Spinozzi F; Department of Life and Environmental Science, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy., Itri R; Instituto de Física, Universidade de São Paulo, Rua do Matão, 1371, São Paulo, SP CEP 05508-090, Brazil., Araujo APU; Instituto de Física de São Carlos, Universidade de São Paulo, Av. João Dagnone, 1100, São Carlos, SP CEP 13563-120, Brazil. Electronic address: anapaula@ifsc.usp.br.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2019 Jul 15; Vol. 133, pp. 428-435. Date of Electronic Publication: 2019 Apr 16.
DOI: 10.1016/j.ijbiomac.2019.04.105
Abstrakt: Septins are members of a group of GTP-binding proteins highly conserved in eukaryotes, being linked to diverse cell processes, such as cytokinesis and membrane association. On the other hand, the malfunction of septins is linked to several pathological processes including neurodegeneration and oncogenesis. Septins interact with each other forming heterocomplexes that polymerize in filaments. Two types of interface between septins alternate along the filament: the G-interface (involving the GTP binding sites), and the NC-interface. This work focuses on the physiological G-interface of SEPT2, used in the SEPT6G-SEPT2G heterodimer assembly, to verify the impact of this interaction on the thermostability and amyloid formation. We found that the SEPT6G-SEPT2G moves to an irreversible state with the ability to bind thioflavin-T at high temperatures, suggesting its amyloid-like nature. Noteworthy, this takes place at a higher temperature than the one observed to the single septins, showing greater thermal/structural stability. Taken together, our results show that in the absence of the partners, the septin becomes unstable and susceptible to amyloid aggregation/formation even in physiological temperatures, and the G-interface appears to have a critical role in this process.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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