Stereochemical features of the envelope protein Domain III of dengue virus reveals putative antigenic site in the five-fold symmetry axis

Author(s)

Soares, R. O. S. ^[1] ; Caliri, A. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Quim & Fis, BR-14040903 Sao Paulo - Brazil

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS; v. 1834, n. 1, p. 221-230, JAN 2013.
• Web of Science Citations: 9

Abstract

We bring to attention a characteristic parasitic pattern present in the dengue virus: it undergoes several intensive thermodynamic variations due to host environmental changes, from a vector's digestive tract, through the human bloodstream and intracellular medium. Comparatively, among the known dengue serotypes, we evaluate the effects that these medium variations may induce to the overall structural characteristics of the Domain III of the envelope (E) protein, checking for stereochemical congruences that could lead to the identification of Immunologic relevant regions. We used molecular dynamics and principal component analysis to study the protein in solution, for all four dengue serotypes, under distinct pH and temperature. We stated that, while the core of Domain III is remarkably rigid and effectively unaffected by most of the mentioned intensive variations, the loops account for major and distinguishable flexibilities. Therefore, the rigidity of the Domain III core provides a foothold that projects specifically two of these high flexible loop regions towards the inner face of the envelope pores, which are found at every five-fold symmetry axis of the icosahedron-shaped mature virus. These loops bear a remarkable low identity though with high occurrence of ionizable residues, including histidines. Such stereochemical properties can provide very particular serotype-specific electrostatic surface patterns, suggesting a viral fingerprint region, on which other specific molecules and ions can establish chemical interactions in an induced fit mechanism. We assert that the proposed regions share enough relevant features to qualify for further immunologic and pharmacologic essays, such as target peptide synthesis and phage display using dengue patients' sera. (C) 2012 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 09/08700-6 - Initial viral infection stage: stereo-chemical study of (glico)protein E envelope of the dengue virus
• Grantee: Ricardo Oliveira dos Santos Soares
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 08/11706-3 - Investigation of the molecular mechanisms of the infection processes of human cells by dengue virus
• Grantee: Leo Degreve
• Support Opportunities: Research Projects - Thematic Grants