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-Structure paper
タイトル | A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface. |
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ジャーナル・号・ページ | EMBO Mol Med, Vol. 6, Issue 3, Page 358-371, Year 2014 |
掲載日 | 2014年1月13日 |
著者 | Guntur Fibriansah / Joanne L Tan / Scott A Smith / Adamberage R de Alwis / Thiam-Seng Ng / Victor A Kostyuchenko / Kristie D Ibarra / Jiaqi Wang / Eva Harris / Aravinda de Silva / James E Crowe / Shee-Mei Lok / |
PubMed 要旨 | Dengue virus (DENV), which consists of four serotypes (DENV1-4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue ...Dengue virus (DENV), which consists of four serotypes (DENV1-4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross-reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype-specific and bind to quaternary structure-dependent epitopes. We determined the structure of DENV1 complexed with Fab fragments of a highly potent HMAb 1F4 to 6 Å resolution by cryo-EM. Although HMAb 1F4 appeared to bind to virus and not E proteins in ELISAs in the previous study, our structure showed that the epitope is located within an envelope (E) protein monomer, and not across neighboring E proteins. The Fab molecules bind to domain I (DI), and DI-DII hinge of the E protein. We also showed that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner. The structure reveals the mechanism by which this potent and specific antibody blocks viral infection. |
リンク | EMBO Mol Med / PubMed:24421336 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 6.0 Å |
構造データ | |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRUS / E PROTEINS / NEUTRALIZATION |