Pérez-Mora, S.; Pérez-Ishiwara, D.G.; Salgado-Hernández, S.V.; Medel-Flores, M.O.; Reyes-López, C.A.; Rodríguez, M.A.; Sánchez-Monroy, V.; Gómez-García, M.C. Entamoeba histolytica: In Silico and In Vitro Oligomerization of EhHSTF5 Enhances Its Binding to the HSE of the EhPgp5 Gene Promoter. Int. J. Mol. Sci.2024, 25, 4218.
Pérez-Mora, S.; Pérez-Ishiwara, D.G.; Salgado-Hernández, S.V.; Medel-Flores, M.O.; Reyes-López, C.A.; Rodríguez, M.A.; Sánchez-Monroy, V.; Gómez-García, M.C. Entamoeba histolytica: In Silico and In Vitro Oligomerization of EhHSTF5 Enhances Its Binding to the HSE of the EhPgp5 Gene Promoter. Int. J. Mol. Sci. 2024, 25, 4218.
Pérez-Mora, S.; Pérez-Ishiwara, D.G.; Salgado-Hernández, S.V.; Medel-Flores, M.O.; Reyes-López, C.A.; Rodríguez, M.A.; Sánchez-Monroy, V.; Gómez-García, M.C. Entamoeba histolytica: In Silico and In Vitro Oligomerization of EhHSTF5 Enhances Its Binding to the HSE of the EhPgp5 Gene Promoter. Int. J. Mol. Sci.2024, 25, 4218.
Pérez-Mora, S.; Pérez-Ishiwara, D.G.; Salgado-Hernández, S.V.; Medel-Flores, M.O.; Reyes-López, C.A.; Rodríguez, M.A.; Sánchez-Monroy, V.; Gómez-García, M.C. Entamoeba histolytica: In Silico and In Vitro Oligomerization of EhHSTF5 Enhances Its Binding to the HSE of the EhPgp5 Gene Promoter. Int. J. Mol. Sci. 2024, 25, 4218.
Abstract
Entamoeba histolytica, throughout its lifecycle, encounters a variety of stressful conditions. This parasite possesses Heat Shock Response Elements (HSEs) which are crucial for regulating the ex-pression of various genes, aiding in its adaptation and survival. These HSEs are regulated by Heat Shock Transcription Factors (EhHSTFs). Our research has identified seven such factors in this parasite, designated as EhHSTF1 through EhHSTF7. Significantly, under heat shock condi-tions and in the presence of the antiamoebic compound emetine, EhHSTF5, EhHSTF6, and EhHSTF7 show overexpression, highlighting their essential role in gene response to these stressors. Currently, only EhHSTF7 has been confirmed to recognize the HSE in the promoter of the EhPgp5 gene (HSE_EhPgp5), leaving the binding potential of the other EhHSTFs to HSE yet to be explored. Consequently, our study aimed to examine both in vitro and in silico the oligomeri-zation and binding capabilities of the recombinant EhHSTF5 protein (rEhHSTF5) to HSE_EhPgp5. The in vitro results indicate that the oligomerization of rEhHSTF5 is concentration-dependent, with its dimeric conformation showing a higher affinity for HSE_EhPgp5 than its monomeric state. In silico analysis suggests that the alpha 3 α-helix (α3-helix) of the DNA-binding domain (DBD5) of EhHSTF5 is crucial in binding to the major groove of HSE, primarily through hydro-gen bonding and salt-bridge interactions. In summary, our results highlight the importance of oligomerization in enhancing the affinity of rEhHSTF5 for HSE_EhPgp5 and demonstrate its abil-ity to specifically recognize structural motifs within HSE_EhPgp5. These insights significantly contribute to our understanding of one of the potential molecular mechanisms employed by the parasite to efficiently respond to various stressors, thereby enabling successful adaptation and survival within its host environment.
Medicine and Pharmacology, Epidemiology and Infectious Diseases
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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