AI Article Synopsis

  • Since 2019, SARS-CoV-2 has mutated, leading to various pandemic and epidemic waves that involve changes in its spike protein, which is key for the virus's entry into cells.
  • Researchers studied the spike proteins from variants BA.2.86 and JN.1, discovering structures where ACE2 receptor binds to the spike protein in both up and down conformations.
  • Their findings suggest that the down-conformation of the receptor-binding domain (RBD) is an important intermediate state that helps facilitate the virus's entry, with specific mutations like K356T impacting infectivity and resistance to neutralizing antibodies.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458767PMC
http://dx.doi.org/10.1038/s41467-024-52808-2DOI Listing

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