eLife (Mar 2022)

Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike

  • Marco A Díaz-Salinas,
  • Qi Li,
  • Monir Ejemel,
  • Leonid Yurkovetskiy,
  • Jeremy Luban,
  • Kuang Shen,
  • Yang Wang,
  • James B Munro

DOI
https://doi.org/10.7554/eLife.75433
Journal volume & issue
Vol. 11

Abstract

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells through binding to angiotensin-converting enzyme 2 (ACE2). This interaction is mediated by the receptor-binding domain (RBD) of the viral spike (S) glycoprotein. Structural and dynamic data have shown that S can adopt multiple conformations, which controls the exposure of the ACE2-binding site in the RBD. Here, using single-molecule Förster resonance energy transfer (smFRET) imaging, we report the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and in the presence of the D614G mutation. We find that D614G modulates the energetics of the RBD position in a manner similar to ACE2 binding. We also find that antibodies that target diverse epitopes, including those distal to the RBD, stabilize the RBD in a position competent for ACE2 binding. Parallel solution-based binding experiments using fluorescence correlation spectroscopy (FCS) indicate antibody-mediated enhancement of ACE2 binding. These findings inform on novel strategies for therapeutic antibody cocktails.

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