Moraes, Adolfo H. Simonelli, Luca Pedotti, Mattia Almeida, Fabio C.L. Varani, Luca Valente, Ana P. 2016-01-28 Domain III of dengue virus E protein (DIII) participates in the 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 pHs 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 virus 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 of two dengue virus serotypes revealed many common features but also some possibly unexpected differences. Antibody binding to DIII of dengue virus serotype 4 attenuated the conformational exchange in the epitope region but, surprisingly, generated exchange in other parts of DIII through allosteric effects. application/pdf https://susi.usi.ch/global/documents/318838 https://localhost:5000/ark:/12658/srd1318838 https://susi.usi.ch/documents/318838/files/Moraes_JV_2016.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1128/JVI.02314-15 info:eu-repo/semantics/altIdentifier/ark/12658/srd1318838 info:eu-repo/semantics/openAccess Rights reserved Journal of virology. - 2016, vol. 90, no. 4, p. 1802-1811 info:eu-repo/classification/udc/61 Antibody binding modulates conformational exchange in domain III of dengue virus E protein http://purl.org/coar/resource_type/c_6501