3RKI

Structural basis for immunization with post-fusion RSV F to elicit high neutralizing antibody titers

3RKI の概要

• エントリーDOI: 10.2210/pdb3rki/pdb
• 分子名称: 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)
• 機能のキーワード: fusion protein, viral protein
• 由来する生物種: Human respiratory syncytial virus
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 178230.53

構造登録者

Swanson, K.A.,Settembre, E.C.,Shaw, C.A.,Dey, A.K.,Rappuoli, R.,Mandl, C.W.,Dormitzer, P.D.,Carfi, A. (登録日: 2011-04-18, 公開日: 2011-05-18, 最終更新日: 2024-10-16)

主引用文献

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

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: 21586636
DOI: 10.1073/pnas.1106536108

実験手法

X-RAY DIFFRACTION (3.2 Å)