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

Gadkari, Rupali A and Srinivasan, Narayanaswamy (2010) Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures. In: BMC Structural Biology, 10 .

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Abstract

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 C alpha 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.

Item Type:	Journal Article
Publication:	BMC Structural Biology
Publisher:	Biomed Central Ltd
Additional Information:	Copyright of this article belongs to Biomed Central Ltd.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	18 Oct 2010 07:21
Last Modified:	18 Oct 2010 07:21
URI:	http://eprints.iisc.ac.in/id/eprint/33287

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