Mutations of an antibody binding energy hot spot on domain III of the dengue 2 envelope glycoprotein exploited for neutralization escape

Gregory D. Gromowski, John T. Roehrig, Michael S. Diamond, James Lee, Trevor J. Pitcher, Alan Barrett

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Previous crystallographic studies have identified a total of 11 DENV-2 envelope protein domain III (ED3) residues (K305, F306, K307, V308, V309, K310, I312, Q325, P364, K388, and N390) that interacted, through both side- and main-chain contacts, with the Fab of a dengue virus (DENV) subcomplex-specific neutralizing monoclonal antibody (MAb) 1A1D-2 (Lok et al., 2008). Here, we used DENV-2 recombinant ED3 mutants of the MAb 1A1D-2 structural epitope residues to determine the functional epitope of this MAb. The side-chains of residues K307, K310 and I312 were determined to be functionally critical for MAb binding, and thus constitute a hot spot of binding energy for MAb 1A1D-2 on the DENV-2 ED3. Overall, these findings demonstrate that only a subset of the amino acid residue side-chains within the structural epitope of MAb 1A1D-2 define a functional epitope on the DENV-2 ED3 that is essential for MAb binding and neutralization escape.

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalVirology
Volume407
Issue number2
DOIs
StatePublished - Nov 25 2010

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Dengue
Dengue Virus
Glycoproteins
Monoclonal Antibodies
Mutation
Antibodies
Epitopes
Viral Envelope Proteins
Neutralizing Antibodies
Amino Acids

Keywords

  • Dengue
  • Envelope protein domain 3
  • Monoclonal antibodies
  • Neutralization

ASJC Scopus subject areas

  • Virology
  • Medicine(all)

Cite this

Mutations of an antibody binding energy hot spot on domain III of the dengue 2 envelope glycoprotein exploited for neutralization escape. / Gromowski, Gregory D.; Roehrig, John T.; Diamond, Michael S.; Lee, James; Pitcher, Trevor J.; Barrett, Alan.

In: Virology, Vol. 407, No. 2, 25.11.2010, p. 237-246.

Research output: Contribution to journalArticle

Gromowski, Gregory D. ; Roehrig, John T. ; Diamond, Michael S. ; Lee, James ; Pitcher, Trevor J. ; Barrett, Alan. / Mutations of an antibody binding energy hot spot on domain III of the dengue 2 envelope glycoprotein exploited for neutralization escape. In: Virology. 2010 ; Vol. 407, No. 2. pp. 237-246.
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