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TitleStructural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 8574, Year 2024
Publish dateOct 7, 2024
AuthorsHisano 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 AbstractSince 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 linksNat Commun / PubMed:39375326 / PubMed Central
MethodsEM (single particle)
Resolution2.59 - 4.3 Å
Structure data

EMDB-37910, PDB-8wxl:
Structure of the SARS-CoV-2 BA.2.86 spike glycoprotein (closed state)
Method: EM (single particle) / Resolution: 2.59 Å

EMDB-38459, PDB-8xux:
Structure of the SARS-CoV-2 BA.2.86 spike protein (1-up state)
Method: EM (single particle) / Resolution: 3.32 Å

EMDB-38686, PDB-8xuy:
Structure of SARS-CoV-2 BA.2.86 spike glycoprotein in complex with ACE2 (2-up state)
Method: EM (single particle) / Resolution: 3.14 Å

EMDB-38687, PDB-8xuz:
Structure of SARS-CoV-2 BA.2.86 spike glycoprotein in complex with ACE2 (2-up and 1-down state)
Method: EM (single particle) / Resolution: 3.05 Å

EMDB-38688, PDB-8xv0:
Structure of SARS-CoV-2 BA.2.86 spike RBD in complex with ACE2 (up state)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-38689, PDB-8xv1:
Structure of SARS-CoV-2 BA.2.86 spike RBD in complex with ACE2 (down state)
Method: EM (single particle) / Resolution: 3.05 Å

EMDB-38690, PDB-8xvm:
Structure of SARS-CoV-2 BA.2.86 spike glycoprotein in complex with ACE2 (3-up state)
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-60886, PDB-9iu1:
Structure of SARS-CoV-2 JN.1 spike RBD in complex with ACE2 (up state)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-60904: Structure of SARS-CoV-2 JN.1 spike glycoprotein in complex with ACE2 (2-up state)
Method: EM (single particle) / Resolution: 3.38 Å

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)
Method: EM (single particle) / Resolution: 4.15 Å

EMDB-60906: Structure of SARS-CoV-2 JN.1 spike glycoprotein in complex with ACE2 (2-up and 1-down state)
Method: EM (single particle) / Resolution: 3.39 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / spike protein / glycoprotein / VIRUS / VIRAL PROTEIN/PROTEIN BINDING / VIRAL PROTEIN-PROTEIN BINDING complex

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