6XXV

Crystal Structure of a computationally designed Immunogen S2_1.2 in complex with its elicited antibody C57

Summary for 6XXV

• Entry DOI: 10.2210/pdb6xxv/pdb
• Related: 6S3D 6XWI
• Descriptor: Antibody C57, Heavy Chain, Antibody C57, Light Chain, S2_1.2, ... (4 entities in total)
• Functional Keywords: epitope scaffold, de novo designed protein, immunogen, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 134010.13

Authors

Yang, C.,Sesterhenn, F.,Correia, B.E.,Pojer, F. (deposition date: 2020-01-28, release date: 2020-04-22, Last modification date: 2024-10-23)

Primary citation

Sesterhenn, F.,Yang, C.,Bonet, J.,Cramer, J.T.,Wen, X.,Wang, Y.,Chiang, C.I.,Abriata, L.A.,Kucharska, I.,Castoro, G.,Vollers, S.S.,Galloux, M.,Dheilly, E.,Rosset, S.,Corthesy, P.,Georgeon, S.,Villard, M.,Richard, C.A.,Descamps, D.,Delgado, T.,Oricchio, E.,Rameix-Welti, M.A.,Mas, V.,Ervin, S.,Eleouet, J.F.,Riffault, S.,Bates, J.T.,Julien, J.P.,Li, Y.,Jardetzky, T.,Krey, T.,Correia, B.E.
De novo protein design enables the precise induction of RSV-neutralizing antibodies.
Science, 368:-, 2020

PubMed Abstract: De novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remains a cornerstone for next-generation vaccines. Here, we present a protein design algorithm called TopoBuilder, with which we engineered epitope-focused immunogens displaying complex structural motifs. In both mice and nonhuman primates, cocktails of three de novo-designed immunogens induced robust neutralizing responses against the respiratory syncytial virus. Furthermore, the immunogens refocused preexisting antibody responses toward defined neutralization epitopes. Overall, our design approach opens the possibility of targeting specific epitopes for the development of vaccines and therapeutic antibodies and, more generally, will be applicable to the design of de novo proteins displaying complex functional motifs.

PubMed: 32409444
DOI: 10.1126/science.aay5051

Experimental method

X-RAY DIFFRACTION (2.20116418766 Å)