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TitleMechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody.
Journal, issue, pagesStructure, Vol. 27, Issue 2, Page 253-267.e8, Year 2019
Publish dateFeb 5, 2019
AuthorsMelissa Wirawan / Guntur Fibriansah / Jan K Marzinek / Xin Xiang Lim / Thiam-Seng Ng / Adelene Y L Sim / Qian Zhang / Victor A Kostyuchenko / Jian Shi / Scott A Smith / Chandra S Verma / Ganesh Anand / James E Crowe / Peter J Bond / Shee-Mei Lok /
PubMed AbstractDengue virus (DENV) particles are released from cells in different maturation states. Fully immature DENV (immDENV) is generally non-infectious, but can become infectious when complexed with anti- ...Dengue virus (DENV) particles are released from cells in different maturation states. Fully immature DENV (immDENV) is generally non-infectious, but can become infectious when complexed with anti-precursor membrane (prM) protein antibodies. It is unknown how anti-prM antibody-coated particles can undergo membrane fusion since the prM caps the envelope (E) protein fusion loop. Here, we determined cryoelectron microscopy (cryo-EM) maps of the immDENV:anti-prM complex at different pH values, mimicking the extracellular (pH 8.0) or endosomal (pH 5.0) environments. At pH 5.0, there are two structural classes with fewer antibodies bound than at pH 8.0. These classes may represent different maturation states. Molecular simulations, together with the measured high-affinity pr:antibody interaction (versus the weak pr:E interaction) and also the low pH cryo-EM structures, suggest how antibody:pr complex can dislodge from the E protein at low pH. This exposes the E protein fusion loop enhancing virus interaction with endosomes.
External linksStructure / PubMed:30471923 / PubMed Central
MethodsEM (single particle)
Resolution12.0 - 25.0 Å
Structure data

9649

6idi

EMDB-9649, PDB-6idi:
Cryo-EM structure of Immature Dengue virus serotype 3 in complex with human antibody 1H10 Fab at pH 8.0.
Method: EM (single particle) / Resolution: 12.0 Å

9650

6idk

EMDB-9650, PDB-6idk:
Cryo-EM structure of Immature Dengue virus serotype 3 in complex with human antibody 1H10 Fab at pH 5.0 (Class I particle)
Method: EM (single particle) / Resolution: 25.0 Å

9651

6idl

EMDB-9651, PDB-6idl:
Cryo-EM structure of Immature Dengue virus serotype 3 in complex with human antibody 1H10 Fab at pH 5.0 (Class II particle)
Method: EM (single particle) / Resolution: 25.0 Å

Source
  • homo sapiens (human)
  • dengue virus 3
KeywordsVIRUS / immature dengue virus / human antibody

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