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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Antibodies, Neutralizing, Binding Sites, COVID-19, Humans, Models, Molecular, Mutation, Protein Binding, Protein Conformation, Protein Domains, SARS-CoV-2, Spike Glycoprotein, Coronavirus
Nat Commun
Date: Oct. 07, 2024
Download Curated Data For This Publication
255774
Switch View:
  • Interactions 3