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https://doi.org/10.1038/srep10592
Title: | Understanding Dengue Virus Capsid Protein Interaction with Key Biological Targets | Authors: | Faustino, A.F Martins, I.C Carvalho, F.A Castanho, M.A.R.B Maurer-Stroh, S Santos, N.C |
Keywords: | apolipoprotein E capsid protein mannose 6 phosphate receptor binding protein 1 peptide PLIN3 protein, human protein binding very low density lipoprotein vesicular transport protein amino acid sequence atomic force microscopy chemistry Dengue virus human metabolism molecular dynamics molecular genetics protein secondary structure protein tertiary structure sequence alignment Amino Acid Sequence Apolipoproteins E Capsid Proteins Dengue Virus Humans Lipoproteins, VLDL Microscopy, Atomic Force Molecular Dynamics Simulation Molecular Sequence Data Peptides Perilipin-3 Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Sequence Alignment Vesicular Transport Proteins |
Issue Date: | 2015 | Publisher: | Nature Publishing Group | Citation: | Faustino, A.F, Martins, I.C, Carvalho, F.A, Castanho, M.A.R.B, Maurer-Stroh, S, Santos, N.C (2015). Understanding Dengue Virus Capsid Protein Interaction with Key Biological Targets. Scientific Reports 5 : 10592. ScholarBank@NUS Repository. https://doi.org/10.1038/srep10592 | Rights: | Attribution 4.0 International | Abstract: | 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 ?-helix 4 (APOE?4) and PLIN3 ?-helix 5 (PLIN3?5) sequences, which are also highly superimposable structurally. Interestingly, APOE ?-helical N-terminal sequence and structure superimposes with DENV C ?-helices ?1 and ?2. Moreover, the DENV C hydrophobic cleft can accommodate the structurally analogous APOE?4 and PLIN3?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 ?-helical structures. | Source Title: | Scientific Reports | URI: | https://scholarbank.nus.edu.sg/handle/10635/180454 | ISSN: | 2045-2322 | DOI: | 10.1038/srep10592 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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