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Title | Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1. |
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Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 8574, Year 2024 |
Publish date | Oct 7, 2024 |
Authors | Hisano Yajima / Yuki Anraku / Yu Kaku / Kanako Terakado Kimura / Arnon Plianchaisuk / Kaho Okumura / Yoshiko Nakada-Nakura / Yusuke Atarashi / Takuya Hemmi / Daisuke Kuroda / Yoshimasa Takahashi / Shunsuke Kita / Jiei Sasaki / Hiromi Sumita / / Jumpei Ito / Katsumi Maenaka / Kei Sato / Takao Hashiguchi / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:39375326 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.59 - 4.3 Å |
Structure data | EMDB-37910, PDB-8wxl: EMDB-38459, PDB-8xux: EMDB-38686, PDB-8xuy: EMDB-38687, PDB-8xuz: EMDB-38688, PDB-8xv0: EMDB-38689, PDB-8xv1: EMDB-38690, PDB-8xvm: EMDB-60886, PDB-9iu1: EMDB-60904: Structure of SARS-CoV-2 JN.1 spike glycoprotein in complex with ACE2 (2-up state) EMDB-60905: Structure of SARS-CoV-2 BA.2.86 spike glycoprotein in complex with ACE2 (1 highly-open RBD and 1 partially-open RBD) EMDB-60906: Structure of SARS-CoV-2 JN.1 spike glycoprotein in complex with ACE2 (2-up and 1-down state) |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN / spike protein / glycoprotein / VIRUS / VIRAL PROTEIN/PROTEIN BINDING / VIRAL PROTEIN-PROTEIN BINDING complex |