6OZ9

Ebola virus glycoprotein in complex with EBOV-520 Fab

6OZ9 の概要

• エントリーDOI: 10.2210/pdb6oz9/pdb
• 分子名称: Small secreted glycoprotein sGP, Envelope glycoprotein, EBOV-520 Fab light chain, ... (6 entities in total)
• 機能のキーワード: glycoprotein, antibody, fab, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Ebola virus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 78034.43

構造登録者

Milligan, J.C.,Altman, P.X.,Hui, S.,Hastie, K.M.,Gilchuk, P.,Crowe, J.E.,Saphire, E.O. (登録日: 2019-05-15, 公開日: 2020-03-11, 最終更新日: 2024-10-23)

主引用文献

Gilchuk, P.,Murin, C.D.,Milligan, J.C.,Cross, R.W.,Mire, C.E.,Ilinykh, P.A.,Huang, K.,Kuzmina, N.,Altman, P.X.,Hui, S.,Gunn, B.M.,Bryan, A.L.,Davidson, E.,Doranz, B.J.,Turner, H.L.,Alkutkar, T.,Flinko, R.,Orlandi, C.,Carnahan, R.,Nargi, R.,Bombardi, R.G.,Vodzak, M.E.,Li, S.,Okoli, A.,Ibeawuchi, M.,Ohiaeri, B.,Lewis, G.K.,Alter, G.,Bukreyev, A.,Saphire, E.O.,Geisbert, T.W.,Ward, A.B.,Crowe Jr., J.E.
Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization.
Immunity, 52:388-403.e12, 2020

PubMed Abstract: Structural principles underlying the composition of protective antiviral monoclonal antibody (mAb) cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic mAb cocktail against Ebola virus. We systematically analyzed the antibody repertoire in human survivors and identified a pair of potently neutralizing mAbs that cooperatively bound to the ebolavirus glycoprotein (GP). High-resolution structures revealed that in a two-antibody cocktail, molecular mimicry was a major feature of mAb-GP interactions. Broadly neutralizing mAb rEBOV-520 targeted a conserved epitope on the GP base region. mAb rEBOV-548 bound to a glycan cap epitope, possessed neutralizing and Fc-mediated effector function activities, and potentiated neutralization by rEBOV-520. Remodeling of the glycan cap structures by the cocktail enabled enhanced GP binding and virus neutralization. The cocktail demonstrated resistance to virus escape and protected non-human primates (NHPs) against Ebola virus disease. These data illuminate structural principles of antibody cooperativity with implications for development of antiviral immunotherapeutics.

PubMed: 32023489
DOI: 10.1016/j.immuni.2020.01.001

実験手法

X-RAY DIFFRACTION (3.462 Å)