Back to Search
Start Over
Designed proteins assemble antibodies into modular nanocages.
- Source :
-
Science (New York, N.Y.) [Science] 2021 Apr 02; Vol. 372 (6537). - Publication Year :
- 2021
-
Abstract
- 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.<br /> (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Angiopoietins chemistry
Angiopoietins immunology
Angiopoietins metabolism
Antibodies, Monoclonal chemistry
Antibodies, Monoclonal immunology
Antibodies, Neutralizing chemistry
Antibodies, Neutralizing immunology
Antibodies, Viral chemistry
Antibodies, Viral immunology
B-Lymphocytes immunology
CD40 Antigens chemistry
CD40 Antigens immunology
CD40 Antigens metabolism
Cell Line, Tumor
Cell Proliferation
Computer Simulation
Genes, Synthetic
Humans
Immunoglobulin Fc Fragments chemistry
Lymphocyte Activation
Models, Molecular
Protein Binding
Receptor, TIE-2 metabolism
Receptors, TNF-Related Apoptosis-Inducing Ligand immunology
Receptors, TNF-Related Apoptosis-Inducing Ligand metabolism
SARS-CoV-2 immunology
T-Lymphocytes immunology
T-Lymphocytes physiology
Antibodies chemistry
Antibodies immunology
Nanostructures
Protein Engineering
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 372
- Issue :
- 6537
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 33795432
- Full Text :
- https://doi.org/10.1126/science.abd9994