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-Structure paper
タイトル | Structural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the Glycoprotein Fusion Loop. |
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ジャーナル・号・ページ | Cell Rep, Vol. 24, Issue 10, Page 2723-22732.e4, Year 2018 |
掲載日 | 2018年9月4日 |
著者 | Charles D Murin / Jessica F Bruhn / Zachary A Bornholdt / Jeffrey Copps / Robyn Stanfield / Andrew B Ward / |
PubMed 要旨 | Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack of a molecular understanding of cross-reactive epitopes. The ...Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack of a molecular understanding of cross-reactive epitopes. The antibody ADI-15878 was previously identified from a human survivor of Ebola virus Makona variant (EBOV/Mak) infection. This mAb demonstrated potent neutralizing activity against all known ebolaviruses and provided protection in rodent and ferret models against three ebolavirus species. Here, we describe the unliganded crystal structure of ADI-15878 as well as the cryo-EM structures of ADI-15878 in complex with the EBOV/Mak and Bundibugyo virus (BDBV) glycoproteins (GPs). ADI-15878 binds through an induced-fit mechanism by targeting highly conserved residues in the internal fusion loop (IFL), bridging across GP protomers via the heptad repeat 1 (HR1) region. Our structures provide a more complete description of the ebolavirus immunogenic landscape, as well as a molecular basis for how rare but potent antibodies target conserved filoviral fusion machinery. |
リンク | Cell Rep / PubMed:30184505 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.1 - 4.29 Å |
構造データ | EMDB-8935, PDB-6dzl: EMDB-8936, PDB-6dzm: PDB-6dzn: |
化合物 | ChemComp-NAG: ChemComp-CL: ChemComp-AE3: ChemComp-PG4: ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN / Ebola / antibody / pan-ebolavirus / internal fusion loop / HR1 / glycoprotein / IMMUNE SYSTEM / ADI-15878 / immunotherapeutic / Ebola virus / Bundibugyo virus |