Journal
ELIFE
Volume 11, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.75433
Keywords
virus entry; protein dynamics; single-molecule biophysics; Viruses
Categories
Funding
- UMass Chan Medical School COVID-19 Pandemic Relief Fund
- National Institutes of Health [R37AI147868, R01AI148784, K22CA241362]
- Evergrande COVID-19 Response Fund
- Massachusetts Consortium on Pathogen Readiness
- Worcester Foundation for Biomedical Research
Ask authors/readers for more resources
This study reveals the effects of ACE2 and antibody binding on the conformational dynamics of SARS-CoV-2 spike protein. The D614G mutation and antibodies targeting diverse epitopes are found to modulate the energetics of the receptor-binding domain (RBD) position and enhance ACE2 binding. These findings offer insights into the development of therapeutic antibody cocktails.
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 Forster 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available