NMR investigation of domain III of Dengue virus E protein: antibody binding modulates conformational exchange in the antigen.
 

NMR investigation of domain III of Dengue virus E protein: antibody binding modulates conformational exchange in the antigen.

Related Articles NMR investigation of domain III of Dengue virus E protein: antibody binding modulates conformational exchange in the antigen.

J Virol. 2015 Dec 4;

Authors: Moraes AH, Simonelli L, Pedotti M, Almeida FC, Varani L, Valente AP

Abstract
Domain III of Dengue virus E protein (DIII) participates in recognition of cell receptors and in structural rearrangements required for membrane fusion and ultimately viral infection; furthermore, it contains epitopes for neutralizing antibodies and has been considered a potential vaccination agent. In this work we addressed various structural aspects of DIII and their relevance for both the Dengue virus infection mechanism and antibody recognition. We provided a dynamic description of DIII at physiological and endosomal pH and in complex with the neutralizing human antibody DV32.6. We observed conformational exchange in the isolated DIII, in regions important for the packing of E protein dimers on the viral surface. This conformational diversity is likely to facilitate the partial detachment of DIII from the other E protein domains, which is required to achieve fusion to the host cellular membranes and to expose the epitopes of many anti-DIII antibodies. A comparison of DIII from two Dengue serotypes revealed many common features but also some possibly unexpected differences. Antibody binding to DIII of Dengue serotype 4 attenuated the conformational exchange in the epitope region but, somehow surprisingly, generated exchange in other parts of DIII through allosteric effects.
IMPORTANCE: Many studies have provided extensive structural information on E protein and particularly on DIII, also in complex with antibodies. However, there is very scarce information regarding the molecular dynamics of DIII and almost nothing is available on the dynamics effect of antibody binding, especially at the quantitative level. This work provides one of the very rare descriptions of the effect of antibody binding on antigen dynamics.


PMID: 26637461 [PubMed - as supplied by publisher]



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