Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1

Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The SARS-CoV-2 spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts the up-conformation. However, whether ACE2 also interacts with the RBD in the down-conformation to facilitate the conformational shift to RBD-up remains unclear. Herein, we present the structures of the BA.2.86 and the JN.1 spike proteins bound to ACE2. Notably, we successfully observed the ACE2-bound down-RBD, indicating an intermediate structure before the RBD-up conformation. The wider and mobile angle of RBDs in the up-state provides space for ACE2 to interact with the down-RBD, facilitating the transition to the RBD-up state. The K356T, but not N354-linked glycan, contributes to both of infectivity and neutralizing-antibody evasion in BA.2.86. These structural insights the spike-protein dynamics would help understand the mechanisms underlying SARS-CoV-2 infection and its neutralization.

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Publication Details

Journal
Nature Communications
Published
2024-10-07
DOI
https://doi.org/10.1038/s41467-024-52808-2
Citations
22
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
8.56

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article

Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1

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Nature Communications
SARS-CoV-2 and COVID-19 Research
8.56
article

Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1

Wilaiporn Saikruang, Terumasa Ikeda, Naoko Yasuhara, Ryo Shimizu, Shusuke Kawakubo, Hayato Ito, Arnon Plianchaisuk, Kaoru Usui, Otowa Takahashi, Keita Matsuno, Yoshimasa Takahashi, Rina Hashimoto, Hiromi Mohri, Mika Chiba, Kanako Kimura, Kei Sato, Ayaka Sakamoto, Mako Toyoda, Mami Nagashima, Wenye Li, Ziyi Guo, Shuhei Tsujino, Hiroyuki Asakura, Hesham Nasser, Akatsuki Saito, Yoshitaka Nakata, Yukio Watanabe, Masumi Tsuda, Yukari Nakajima, Alfredo A. Hinay, Kyoko Yasuda, Shiho Tanaka, Keita Mizuma, Yuma Ohari, Isao Yoshida, Yuki Anraku, Takasuke Fukuhara, Chihiro Motozono, Kaho Okumura, Katsumi Maenaka, Mai Suganami, Kazuo Takayama, Izumi Kida, Yoshiko Nakada-Nakura, Lin Pan, Jiei Sasaki, Aditi Konar, Miki Kawano, Tomokazu Tamura, Naganori Nao, Jarel Elgin Tolentino, So Nakagawa, Shinya Tanaka, Shigeru Fujita, Yusuke Atarashi, Kaori Sasaki‐Tabata, Jumpei Ito, Jingshu Li, Kenji Shishido, Tateki Suzuki, Takamasa Ueno, Sayaka Deguchi, Ryoko Kawabata, Michael Jonathan, Rigel Suzuki, Takao Hashiguchi, Jiří Zahradník, Naoko Misawa, Miguel Padilla‐Blanco, Shunsuke Kita, Ryo Yoshimura, Tomoko Nishiuchi, Takuya Hemmi, Daisuke Kuroda, Naomi Ohsumi, Yuka Mugita, Hiroki Futatsusako, Prokopios Andrikopoulos, Spyridon Lytras, Luca Nishumura, Maximilian Stanley Yo, Kio Horinaka, Rina Osujo, Chen Luo, Zannatul Ferdous, Keiko Iida, Saori Suzuki, Kenji Sadamas, Miki Iida, Hiromi Sumita, Yu Kaku, Kazuhisa Yoshimura, Hisano Yajima, E. Ogawa, Yusuke Kosugi, Sharee Leong, Adam Strange, Yume Mimura, Hirofumi Sawa, Anon Kosaka, Yoshikata Oda, T Fukuda, N Matsubara, M. S. T. Monira Begum, Takashi Irie, Keiya Uriu, Lei Wang
article en
22 citations

Abstract

Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The SARS-CoV-2 spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts the up-conformation. However, whether ACE2 also interacts with the RBD in the down-conformation to facilitate the conformational shift to RBD-up remains unclear. Herein, we present the structures of the BA.2.86 and the JN.1 spike proteins bound to ACE2. Notably, we successfully observed the ACE2-bound down-RBD, indicating an intermediate structure before the RBD-up conformation. The wider and mobile angle of RBDs in the up-state provides space for ACE2 to interact with the down-RBD, facilitating the transition to the RBD-up state. The K356T, but not N354-linked glycan, contributes to both of infectivity and neutralizing-antibody evasion in BA.2.86. These structural insights the spike-protein dynamics would help understand the mechanisms underlying SARS-CoV-2 infection and its neutralization.

Nature CommunicationsVol. 15(1)
Hiroshima University (JP), University of Miyazaki (JP), Tokai University (JP), Kyushu University (JP), Hokkaido University (JP), Charles University (CZ), Kyoto University (JP), Kyoto Medical Center (JP), National Institute of Infectious Diseases (JP), Japan Science and Technology Agency (JP), Tokyo Metropolitan Institute of Public Health (JP), Shinjuku Yamabuki High School (JP), Saitama International Medical Center (JP), MRC University of Glasgow Centre for Virus Research (GB), Sophia University (JP), The University of Tokyo (JP), Kumamoto University (JP)
Naito Foundation, Japan Agency for Medical Research and Development, Ministry of Education, Culture, Sports, Science and Technology, University of Tokyo, Hokkaido University, Japan Society for the Promotion of Science, Institute of Medical Science, University of Tokyo, Core Research for Evolutional Science and Technology
Openalex Percentile: Top 2%
SARS-CoV-2 and COVID-19 Research
8.56
DOIOpen Access PDFOpenAlex
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