Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/23504
Título: Understanding Dengue virus capsid protein interaction with key biological targets
Autor: Faustino, André F.
Martins, Ivo C.
Carvalho, Filomena A.
Castanho, Miguel A. R. B.
Maurer-Stroh, Sebastian
Santos, Nuno C.
Data: 2015
Editora: Nature Publishing Group
Citação: Sci. Rep. 5, 10592
Resumo: Dengue virus (DENV) causes over 500,000 hospitalizations and 20,000 deaths worldwide every year. Dengue epidemics now reach temperate regions due to globalization of trade and travel and climate changes. Currently, there are no successful therapeutic or preventive approaches. We previously developed a peptide drug lead, pep14-23, that inhibits the biologically relevant interaction of DENV capsid (C) protein with lipid droplets (LDs). Surprisingly, pep14-23 also inhibits DENV C interaction with very low-density lipoproteins (VLDL). We thus investigated the similarity between the proposed DENV C molecular targets in LDs and VLDL, respectively, the proteins perilipin 3 (PLIN3) and apolipoprotein E (APOE). APOE N-terminal and PLIN3 C-terminal regions are remarkably similar, namely APOE α -helix 4 (APOEα 4) and PLIN3 α -helix 5 (PLIN3α 5) sequences, which are also highly superimposable structurally. Interestingly, APOE α -helical N-terminal sequence and structure superimposes with DENV C α -helices α 1 and α 2. Moreover, the DENV C hydrophobic cleft can accommodate the structurally analogous APOEα 4 and PLIN3α 5 helical regions. Mirroring DENV C-LDs interaction (previously shown experimentally to require PLIN3), we experimentally demonstrated that DENV C-VLDL interaction requires APOE. Thus, the results fit well with previous data and suggest future drug development strategies targeting the above mentioned α –helical structures.
Descrição: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Supplementary information accompanies this paper at http://www.nature.com/srep
Peer review: yes
URI: http://hdl.handle.net/10451/23504
DOI: 10.1038/srep10592
ISSN: 2045-2322
Versão do Editor: http://www.nature.com/srep/
Aparece nas colecções:IMM - Artigos em Revistas Internacionais

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