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-Structure paper
タイトル | Structures of Ebola virus GP and sGP in complex with therapeutic antibodies. |
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ジャーナル・号・ページ | Nat Microbiol, Vol. 1, Issue 9, Page 16128, Year 2016 |
掲載日 | 2016年8月8日 |
著者 | Jesper Pallesen / Charles D Murin / Natalia de Val / Christopher A Cottrell / Kathryn M Hastie / Hannah L Turner / Marnie L Fusco / Andrew I Flyak / Larry Zeitlin / James E Crowe / Kristian G Andersen / Erica Ollmann Saphire / Andrew B Ward / |
PubMed 要旨 | The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little ...The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene. |
リンク | Nat Microbiol / PubMed:27562261 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.3 - 5.5 Å |
構造データ | EMDB-8240: EBOV GP in complex with IgG c2G4 and c13C6 Fabs |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / Ebola virus surface glycoprotein / therapeutic antibody cocktail / ZMapp / VIRAL PROTEIN-IMMUNE SYSTEM complex / Ebola virus secreted glycoprotein / sGP / antibodies |