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-Structure paper
タイトル | Designed proteins assemble antibodies into modular nanocages. |
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ジャーナル・号・ページ | Science, Vol. 372, Issue 6537, Year 2021 |
掲載日 | 2021年4月2日 |
著者 | Robby Divine / Ha V Dang / George Ueda / Jorge A Fallas / Ivan Vulovic / William Sheffler / Shally Saini / Yan Ting Zhao / Infencia Xavier Raj / Peter A Morawski / Madeleine F Jennewein / Leah J Homad / Yu-Hsin Wan / Marti R Tooley / Franziska Seeger / Ali Etemadi / Mitchell L Fahning / James Lazarovits / Alex Roederer / Alexandra C Walls / Lance Stewart / Mohammadali Mazloomi / Neil P King / Daniel J Campbell / Andrew T McGuire / Leonidas Stamatatos / Hannele Ruohola-Baker / Julie Mathieu / David Veesler / David Baker / |
PubMed 要旨 | Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by ...Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)-mediated apoptosis, angiopoietin-1 receptor (Tie2)-mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc-angiotensin-converting enzyme 2 (ACE2) fusion proteins. |
リンク | Science / PubMed:33795432 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 11.0 - 12.0 Å |
構造データ | EMDB-23265: EMDB-23266: |
由来 |
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