3RKI
Structural basis for immunization with post-fusion RSV F to elicit high neutralizing antibody titers
Summary for 3RKI
| Entry DOI | 10.2210/pdb3rki/pdb |
| Descriptor | Fusion glycoprotein F0, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | fusion protein, viral protein |
| Biological source | Human respiratory syncytial virus |
| Total number of polymer chains | 3 |
| Total formula weight | 178230.53 |
| Authors | Swanson, K.A.,Settembre, E.C.,Shaw, C.A.,Dey, A.K.,Rappuoli, R.,Mandl, C.W.,Dormitzer, P.D.,Carfi, A. (deposition date: 2011-04-18, release date: 2011-05-18, Last modification date: 2024-10-16) |
| Primary citation | Swanson, K.A.,Settembre, E.C.,Shaw, C.A.,Dey, A.K.,Rappuoli, R.,Mandl, C.W.,Dormitzer, P.R.,Carfi, A. Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers. Proc.Natl.Acad.Sci.USA, 108:9619-9624, 2011 Cited by PubMed Abstract: Respiratory syncytial virus (RSV), the main cause of infant bronchiolitis, remains a major unmet vaccine need despite more than 40 years of vaccine research. Vaccine candidates based on a chief RSV neutralization antigen, the fusion (F) glycoprotein, have foundered due to problems with stability, purity, reproducibility, and potency. Crystal structures of related parainfluenza F glycoproteins have revealed a large conformational change between the prefusion and postfusion states, suggesting that postfusion F antigens might not efficiently elicit neutralizing antibodies. We have generated a homogeneous, stable, and reproducible postfusion RSV F immunogen that elicits high titers of neutralizing antibodies in immunized animals. The 3.2-Å X-ray crystal structure of this substantially complete RSV F reveals important differences from homology-based structural models. Specifically, the RSV F crystal structure demonstrates the exposure of key neutralizing antibody binding sites on the surface of the postfusion RSV F trimer. This unanticipated structural feature explains the engineered RSV F antigen's efficiency as an immunogen. This work illustrates how structural-based antigen design can guide the rational optimization of candidate vaccine antigens. PubMed: 21586636DOI: 10.1073/pnas.1106536108 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
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