tetano
Editor, Senior Moderator
Elife
. 2022 Mar 24;11:e75433.
doi: 10.7554/eLife.75433. Online ahead of print.
Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike
Marco A Diaz-Salinas[SUP] 1 [/SUP], Qi Li[SUP] 1 [/SUP], Monir Ejemel[SUP] 1 [/SUP], Leonid Yurkovetskiy[SUP] 2 [/SUP], Jeremy Luban[SUP] 2 [/SUP], Kuang Shen[SUP] 2 [/SUP], Yang Wang[SUP] 2 [/SUP], James B Munro[SUP] 1 [/SUP]
Affiliations
Abstract
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.
Keywords: infectious disease; microbiology; molecular biophysics; structural biology; viruses.
. 2022 Mar 24;11:e75433.
doi: 10.7554/eLife.75433. Online ahead of print.
Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike
Marco A Diaz-Salinas[SUP] 1 [/SUP], Qi Li[SUP] 1 [/SUP], Monir Ejemel[SUP] 1 [/SUP], Leonid Yurkovetskiy[SUP] 2 [/SUP], Jeremy Luban[SUP] 2 [/SUP], Kuang Shen[SUP] 2 [/SUP], Yang Wang[SUP] 2 [/SUP], James B Munro[SUP] 1 [/SUP]
Affiliations
- PMID: 35323111
- DOI: 10.7554/eLife.75433
Abstract
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.
Keywords: infectious disease; microbiology; molecular biophysics; structural biology; viruses.