National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI011219
米国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2017 タイトル: Antibody-induced uncoating of human rhinovirus B14. 著者: Yangchao Dong / Yue Liu / Wen Jiang / Thomas J Smith / Zhikai Xu / Michael G Rossmann / 要旨: Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigen-binding (Fab) ...Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigen-binding (Fab) fragment of a neutralizing antibody (C5) can trigger genome release from RV-B14 to form emptied particles and neutralize virus infection. Using cryo-electron microscopy, structures of the C5 Fab in complex with the full and emptied particles have been determined at 2.3 Å and 3.0 Å resolution, respectively. Each of the 60 Fab molecules binds primarily to a region on viral protein 3 (VP3). Binding of the C5 Fabs to RV-B14 results in significant conformational changes around holes in the capsid through which the viral RNA might exit. These results are so far the highest resolution view of an antibody-virus complex and elucidate a mechanism whereby antibodies neutralize RVs and related viruses by inducing virus uncoating.
名称: Human rhinovirus B14 / タイプ: virus / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Viruses were grown in HeLa-H1 cells. Full virions were converted into empty particles upon binding to Fab fragments. NCBI-ID: 12131 / 生物種: Human rhinovirus B14 / ウイルスタイプ: VIRUS-LIKE PARTICLE / ウイルス・単離状態: STRAIN / ウイルス・エンベロープ: No / ウイルス・中空状態: Yes
ソフトウェア - 名称: RELION (ver. 1.4) 詳細: 9521 particles were selected after 2D classification.
FSC曲線 (解像度の算出)
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原子モデル構築 1
詳細
A combination of the following approaches was used: (1) model rebuilding using Coot, (2) real space refinement using Phenix, (3) reciprocal space refinment using Phenix (as in standard crystallographic refinement).
精密化
空間: REAL / プロトコル: RIGID BODY FIT / 当てはまり具合の基準: correlation coefficient
得られたモデル
PDB-5w3o: CryoEM structure of rhinovirus B14 in complex with C5 Fab (33 degrees Celsius, molar ratio 1:3, empty particle)