Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures

Gadkari, Rupali A.; Srinivasan, Narayanaswamy
January 2010
BMC Structural Biology;2010, Vol. 10, p17
Academic Journal
Background: Dengue virus along with the other members of the flaviviridae family has reemerged as deadly human pathogens. Understanding the mechanistic details of these infections can be highly rewarding in developing effective antivirals. During maturation of the virus inside the host cell, the coat proteins E and M undergo conformational changes, altering the morphology of the viral coat. However, due to low resolution nature of the available 3-D structures of viral assemblies, the atomic details of these changes are still elusive. Results: In the present analysis, starting from Ca positions of low resolution cryo electron microscopic structures the residue level details of protein-protein interaction interfaces of dengue virus coat proteins have been predicted. By comparing the preexisting structures of virus in different phases of life cycle, the changes taking place in these predicted protein-protein interaction interfaces were followed as a function of maturation process of the virus. Besides changing the current notion about the presence of only homodimers in the mature viral coat, the present analysis indicated presence of a proline-rich motif at the protein-protein interaction interface of the coat protein. Investigating the conservation status of these seemingly functionally crucial residues across other members of flaviviridae family enabled dissecting common mechanisms used for infections by these viruses. Conclusions: Thus, using computational approach the present analysis has provided better insights into the preexisting low resolution structures of virus assemblies, the findings of which can be made use of in designing effective antivirals against these deadly human pathogens.


Related Articles

  • Guanylate-binding protein 1 participates in cellular antiviral response to dengue virus. Wen Pan; Xiangyang Zuo; Tingting Feng; Xiaohong Shi; Jianfeng Dai // Virology Journal;2012, Vol. 9 Issue 1, p292 

    Background: Dengue virus (DENV), the causative agent of human Dengue hemorrhagic fever, is a mosquito-borne virus found in tropical and sub-tropical regions around the world. Vaccines against DENV are currently unavailable. Guanylate-binding protein 1 (GBP1) is one of the Interferon (IFN)...

  • Dengue Virus Capsid Protein Usurps Lipid Droplets for Viral Particle Formation. Samsa, Marcelo M.; Mondotte, Juan A.; Iglesias, Nestor G.; Assunção-Miranda, Iranaia; Barbosa-Lima, Giselle; Da Poian, Andrea T.; Bozza, Patricia T.; Gamarnik, Andrea V. // PLoS Pathogens;Oct2009, Vol. 5 Issue 10, p1 

    Dengue virus is responsible for the highest rates of disease and mortality among the members of the Flavivirus genus. Dengue epidemics are still occurring around the world, indicating an urgent need of prophylactic vaccines and antivirals. In recent years, a great deal has been learned about the...

  • In silico Molecular Modelling and Docking Studies on Therapeutic Target Non Structural Protein 3 (NS3) of Dengue Virus 1. Komala, Sakamoori; Ravi, Sahukari; Usnantaj, Patan; Shanmugam, Bhasha; Subbaiah, Ganjikunta Venkata; Reddy, Kesireddy Sathyavelu // International Journal of Pharmaceutical Sciences Review & Resear;Nov/Dec2014, Vol. 29 Issue 1, p37 

    Dengue virus (DENV) is a family member of flaviviruses, transfer their pathogenecity to humans by the vector mosquitoes and it is showing similar positive sense genomic RNA as such flavivirus, encodes single polyprotein in order to synthesize structural and non structural proteins. Non...

  • Dengue Virus NS5 Inhibits Interferon-a Signaling by Blocking Signal Transducer and Activator of Transcription 2 Phosphorylation. Mazzon, Michela; Jones, Meleri; Davidson, Andrew; Chain, Benjamin; Jacobs, Michael // Journal of Infectious Diseases;10/15/2009, Vol. 200 Issue 8, p1261 

    Type I interferons (interferon [IFN]-α/β) are key mediators of innate antiviral responses. Inhibition of IFN-mediated signal transduction by dengue viruses (DENVs), mosquito-borne flaviviruses of immense global health importance, probably plays a crucial role in determining the outcome of...

  • Immature Dengue Virus: A Veiled Pathogen? Rodenhuis-Zybert, Izabela A.; van der Schaar, Hilde M.; da Silva Voorham, Júlia M.; van der Ende-Metselaar, Heidi; Huan-Yao Lei; Wilschut, Jan; Smit, Jolanda M. // PLoS Pathogens;Jan2010, Vol. 6 Issue 1, p1 

    Cells infected with dengue virus release a high proportion of immature prM-containing virions. In accordance, substantial levels of prM antibodies are found in sera of infected humans. Furthermore, it has been recently described that the rates of prM antibody responses are significantly higher...

  • Immunopathogenesis of Dengue Virus Infection. Huan-Yao Lei; Trai-Ming Yeh, Julie Y. H.; Hsiao-Sheng Liu; Yee-Shin Lin; Shun-Hua Chen; Ching-Chuan Liu // Journal of Biomedical Science;2001, Vol. 8 Issue 5, p377 

    Dengue virus infection causes dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), whose pathogeneses are not clearly understood. Current hypotheses of antibody-dependent enhancement, virus virulence, and IFN-γ/TNFα-mediated immunopathogenesis are...

  • In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions.  // PLoS Pathogens;Oct2010, Vol. 6 Issue 10, p1 

    No abstract available.

  • Modulation of enzymatic activity of dengue virus nonstructural protein NS3 nucleoside triphosphatase/helicase by poly(U). Junaid, M.; Angsuthanasombat, C.; Wikberg, J.; Ali, N.; Katzenmeier, G. // Biochemistry (00062979);Aug2013, Vol. 78 Issue 8, p925 

    The nonstructural protein 3 (NS3) appears to be the most promising target for anti-flavivirus therapy because of its multiple enzymatic activities that are indispensable for virus replication. NS3 of dengue virus type 2 (DEN2) is composed of two domains, a serine protease in the N-terminal...

  • Advances in the development of vaccines for dengue fever. Simmons, Monika; Teneza-Mora, Nimfa; Putnak, Robert // Vaccine: Development & Therapy;2012, Vol. 2, p1 

    Dengue fever is caused by the mosquito-borne dengue virus (DENV) serotypes 1-4, and is the most common arboviral infection of humans in subtropical and tropical regions of the world. There are currently no prophylaxis or treatment options in the form of vaccines or antivirals, leaving vector...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics