Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions [v3; ref status: indexed, http://f1000r.es/50u]
Ebola, considered till recently as a rare and endemic disease, has dramatically transformed into a potentially global humanitarian crisis. The genome of Ebola, a member of the Filoviridae family, encodes seven proteins. Based on the recently implemented software (PAGAL) for analyzing the hydrophobic...
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F1000 Research Ltd
2015-01-01
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| Online Access: | http://f1000research.com/articles/3-251/v3 |
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| author | Sandeep Chakraborty Basuthkar J. Rao Bjarni Asgeirsson Abhaya Dandekar |
| author_facet | Sandeep Chakraborty Basuthkar J. Rao Bjarni Asgeirsson Abhaya Dandekar |
| author_sort | Sandeep Chakraborty |
| collection | DOAJ |
| description | Ebola, considered till recently as a rare and endemic disease, has dramatically transformed into a potentially global humanitarian crisis. The genome of Ebola, a member of the Filoviridae family, encodes seven proteins. Based on the recently implemented software (PAGAL) for analyzing the hydrophobicity and amphipathicity properties of alpha helices (AH) in proteins, we characterize the helices in the Ebola proteome. We demonstrate that AHs with characteristically unique features are involved in critical interactions with the host proteins. For example, the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain has an AH with a large hydrophobic moment. The neutralizing antibody (KZ52) derived from a human survivor of the 1995 Kikwit outbreak recognizes a protein epitope on this AH, emphasizing the critical nature of this secondary structure in the virulence of the Ebola virus. Our method ensures a comprehensive list of such `hotspots'. These helices probably are or can be the target of molecules designed to inhibit AH mediated protein-protein interactions. Further, by comparing the AHs in proteins of the related Marburg viruses, we are able to elicit subtle changes in the proteins that might render them ineffective to previously successful drugs. Such differences are difficult to identify by a simple sequence or structural alignment. Thus, analyzing AHs in the small Ebola proteome can aid rational design aimed at countering the `largest Ebola epidemic, affecting multiple countries in West Africa' (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html). |
| first_indexed | 2024-12-11T08:52:43Z |
| format | Article |
| id | doaj.art-50d59dfa43d44fc79ad544bdc82153ab |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-11T08:52:43Z |
| publishDate | 2015-01-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-50d59dfa43d44fc79ad544bdc82153ab2022-12-22T01:13:58ZengF1000 Research LtdF1000Research2046-14022015-01-01310.12688/f1000research.5573.36510Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions [v3; ref status: indexed, http://f1000r.es/50u]Sandeep Chakraborty0Basuthkar J. Rao1Bjarni Asgeirsson2Abhaya Dandekar3Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai, 400 005, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai, 400 005, IndiaScience Institute, Department of Biochemistry, University of Iceland, Dunhaga 3, IS-107 Reykjavik, IcelandPlant Sciences Department, University of California, Davis, 95616, USAEbola, considered till recently as a rare and endemic disease, has dramatically transformed into a potentially global humanitarian crisis. The genome of Ebola, a member of the Filoviridae family, encodes seven proteins. Based on the recently implemented software (PAGAL) for analyzing the hydrophobicity and amphipathicity properties of alpha helices (AH) in proteins, we characterize the helices in the Ebola proteome. We demonstrate that AHs with characteristically unique features are involved in critical interactions with the host proteins. For example, the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain has an AH with a large hydrophobic moment. The neutralizing antibody (KZ52) derived from a human survivor of the 1995 Kikwit outbreak recognizes a protein epitope on this AH, emphasizing the critical nature of this secondary structure in the virulence of the Ebola virus. Our method ensures a comprehensive list of such `hotspots'. These helices probably are or can be the target of molecules designed to inhibit AH mediated protein-protein interactions. Further, by comparing the AHs in proteins of the related Marburg viruses, we are able to elicit subtle changes in the proteins that might render them ineffective to previously successful drugs. Such differences are difficult to identify by a simple sequence or structural alignment. Thus, analyzing AHs in the small Ebola proteome can aid rational design aimed at countering the `largest Ebola epidemic, affecting multiple countries in West Africa' (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html).http://f1000research.com/articles/3-251/v3Protein Chemistry & ProteomicsTheory & SimulationTropical & Travel-Associated DiseasesVirology |
| spellingShingle | Sandeep Chakraborty Basuthkar J. Rao Bjarni Asgeirsson Abhaya Dandekar Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions [v3; ref status: indexed, http://f1000r.es/50u] F1000Research Protein Chemistry & Proteomics Theory & Simulation Tropical & Travel-Associated Diseases Virology |
| title | Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions [v3; ref status: indexed, http://f1000r.es/50u] |
| title_full | Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions [v3; ref status: indexed, http://f1000r.es/50u] |
| title_fullStr | Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions [v3; ref status: indexed, http://f1000r.es/50u] |
| title_full_unstemmed | Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions [v3; ref status: indexed, http://f1000r.es/50u] |
| title_short | Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions [v3; ref status: indexed, http://f1000r.es/50u] |
| title_sort | characterizing alpha helical properties of ebola viral proteins as potential targets for inhibition of alpha helix mediated protein protein interactions v3 ref status indexed http f1000r es 50u |
| topic | Protein Chemistry & Proteomics Theory & Simulation Tropical & Travel-Associated Diseases Virology |
| url | http://f1000research.com/articles/3-251/v3 |
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