1. Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1.
- Author
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Yajima H, Anraku Y, Kaku Y, Kimura KT, Plianchaisuk A, Okumura K, Nakada-Nakura Y, Atarashi Y, Hemmi T, Kuroda D, Takahashi Y, Kita S, Sasaki J, Sumita H, Ito J, Maenaka K, Sato K, and Hashiguchi T
- Subjects
- Humans, Mutation, Antibodies, Neutralizing immunology, Binding Sites, Protein Conformation, Models, Molecular, Spike Glycoprotein, Coronavirus metabolism, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus genetics, SARS-CoV-2 metabolism, SARS-CoV-2 chemistry, Angiotensin-Converting Enzyme 2 metabolism, Angiotensin-Converting Enzyme 2 chemistry, Protein Binding, COVID-19 virology, COVID-19 metabolism, Protein Domains
- 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., (© 2024. The Author(s).)
- Published
- 2024
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