Japan Agency for Medical Research and Development (AMED)
JP19fk0108161
日本
Japan Agency for Medical Research and Development (AMED)
JP20nf0101623
日本
Japan Agency for Medical Research and Development (AMED)
JP20nk0101602
日本
Japan Agency for Medical Research and Development (AMED)
JP17am0101108
日本
Ministry of Education, Culture, Sports, Science and Technology (Japan)
JP19H04808
日本
Japan Society for the Promotion of Science (JSPS)
JP18H05279
日本
Japan Society for the Promotion of Science (JSPS)
JP19H03478
日本
引用
ジャーナル: Cell / 年: 2021 タイトル: An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies. 著者: Yafei Liu / Wai Tuck Soh / Jun-Ichi Kishikawa / Mika Hirose / Emi E Nakayama / Songling Li / Miwa Sasai / Tatsuya Suzuki / Asa Tada / Akemi Arakawa / Sumiko Matsuoka / Kanako Akamatsu / ...著者: Yafei Liu / Wai Tuck Soh / Jun-Ichi Kishikawa / Mika Hirose / Emi E Nakayama / Songling Li / Miwa Sasai / Tatsuya Suzuki / Asa Tada / Akemi Arakawa / Sumiko Matsuoka / Kanako Akamatsu / Makoto Matsuda / Chikako Ono / Shiho Torii / Kazuki Kishida / Hui Jin / Wataru Nakai / Noriko Arase / Atsushi Nakagawa / Maki Matsumoto / Yukoh Nakazaki / Yasuhiro Shindo / Masako Kohyama / Keisuke Tomii / Koichiro Ohmura / Shiro Ohshima / Toru Okamoto / Masahiro Yamamoto / Hironori Nakagami / Yoshiharu Matsuura / Atsushi Nakagawa / Takayuki Kato / Masato Okada / Daron M Standley / Tatsuo Shioda / Hisashi Arase / 要旨: Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection. However, the effects of antibodies against other spike protein domains are largely ...Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection. However, the effects of antibodies against other spike protein domains are largely unknown. Here, we screened a series of anti-spike monoclonal antibodies from coronavirus disease 2019 (COVID-19) patients and found that some of antibodies against the N-terminal domain (NTD) induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2. Mutational analysis revealed that all of the infectivity-enhancing antibodies recognized a specific site on the NTD. Structural analysis demonstrated that all infectivity-enhancing antibodies bound to NTD in a similar manner. The antibodies against this infectivity-enhancing site were detected at high levels in severe patients. Moreover, we identified antibodies against the infectivity-enhancing site in uninfected donors, albeit at a lower frequency. These findings demonstrate that not only neutralizing antibodies but also enhancing antibodies are produced during SARS-CoV-2 infection.
電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k)
-
解析
EMソフトウェア
ID
名称
バージョン
カテゴリ
詳細
Fitting-ID
1
cryoSPARC
3.0.1
粒子像選択
2
SerialEM
画像取得
4
cryoSPARC
3.0.1
CTF補正
7
UCSF Chimera
モデルフィッティング
Thesoftwarewasusedforrigidbodyfitting.
1
9
cryoSPARC
3.0.1
初期オイラー角割当
10
cryoSPARC
3.0.1
最終オイラー角割当
11
cryoSPARC
3.0.1
分類
12
cryoSPARC
3.0.1
3次元再構成
CTF補正
タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION
粒子像の選択
選択した粒子像数: 2135
対称性
点対称性: C1 (非対称)
3次元再構成
解像度: 3.53 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 169524 / アルゴリズム: FOURIER SPACE / 対称性のタイプ: POINT
原子モデル構築
ID
プロトコル
空間
Target criteria
詳細
1
RIGIDBODYFIT
REAL
correlation
The protein was homology modeled using MODELLER software. Then, the model was fitted into Cryo-EM map. The loop region of NTD was remodeled by MODELLER.