Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike.
Marco Aurelio Díaz-SalinasQi LiMonir EjemelLeonid YurkovetskiyJeremy LubanKuang ShenYang WangJames B MunroPublished in: eLife (2022)
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.
Keyphrases
- angiotensin converting enzyme
- single molecule
- energy transfer
- sars cov
- angiotensin ii
- respiratory syndrome coronavirus
- dna binding
- binding protein
- coronavirus disease
- high resolution
- quantum dots
- small molecule
- induced apoptosis
- living cells
- oxidative stress
- molecular dynamics
- transcription factor
- molecular dynamics simulations
- mass spectrometry
- signaling pathway
- machine learning
- cell death
- cell proliferation
- electronic health record
- photodynamic therapy