tetano
Editor, Senior Moderator
Nat Commun
. 2024 Oct 7;15(1):8574.
doi: 10.1038/s41467-024-52808-2. Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1
Hisano Yajima[SUP] 1 [/SUP], Yuki Anraku[SUP] 2 [/SUP], Yu Kaku[SUP] 3 [/SUP], Kanako Terakado Kimura[SUP] 1 [/SUP], Arnon Plianchaisuk[SUP] 3 [/SUP], Kaho Okumura[SUP] 3 4 [/SUP], Yoshiko Nakada-Nakura[SUP] 1 [/SUP], Yusuke Atarashi[SUP] 1 5 [/SUP], Takuya Hemmi[SUP] 1 [/SUP], Daisuke Kuroda[SUP] 5 [/SUP], Yoshimasa Takahashi[SUP] 5 6 [/SUP], Shunsuke Kita[SUP] 2 [/SUP], Jiei Sasaki[SUP] 1 [/SUP], Hiromi Sumita[SUP] 7 [/SUP]; Genotype to Phenotype Japan (G2P-Japan) Consortium; Jumpei Ito[SUP] 3 8 [/SUP], Katsumi Maenaka[SUP] 2 6 9 10 11 [/SUP], Kei Sato[SUP] 12 13 14 15 16 17 18 19 [/SUP], Takao Hashiguchi[SUP] 20 21 22 [/SUP]
Collaborators, Affiliations
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 Oct 7;15(1):8574.
doi: 10.1038/s41467-024-52808-2. Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1
Hisano Yajima[SUP] 1 [/SUP], Yuki Anraku[SUP] 2 [/SUP], Yu Kaku[SUP] 3 [/SUP], Kanako Terakado Kimura[SUP] 1 [/SUP], Arnon Plianchaisuk[SUP] 3 [/SUP], Kaho Okumura[SUP] 3 4 [/SUP], Yoshiko Nakada-Nakura[SUP] 1 [/SUP], Yusuke Atarashi[SUP] 1 5 [/SUP], Takuya Hemmi[SUP] 1 [/SUP], Daisuke Kuroda[SUP] 5 [/SUP], Yoshimasa Takahashi[SUP] 5 6 [/SUP], Shunsuke Kita[SUP] 2 [/SUP], Jiei Sasaki[SUP] 1 [/SUP], Hiromi Sumita[SUP] 7 [/SUP]; Genotype to Phenotype Japan (G2P-Japan) Consortium; Jumpei Ito[SUP] 3 8 [/SUP], Katsumi Maenaka[SUP] 2 6 9 10 11 [/SUP], Kei Sato[SUP] 12 13 14 15 16 17 18 19 [/SUP], Takao Hashiguchi[SUP] 20 21 22 [/SUP]
Collaborators, Affiliations
- PMID: 39375326
- DOI: 10.1038/s41467-024-52808-2
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.