Structural impact on SARS-CoV-2 spike protein by D614G substitution.
Substitution for aspartic acid (D) by glycine (G) at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. Here, we report cryo-electron microscopy structures of ... a full-length G614 S trimer, which adopts three distinct prefusion conformations that differ primarily by the position of one receptor-binding domain. A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer-effectively increasing the number of functional spikes and enhancing infectivity-and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.
Mesh Terms:
Amino Acid Substitution, Angiotensin-Converting Enzyme 2, Antibodies, Viral, COVID-19, Cryoelectron Microscopy, Humans, Hydrophobic and Hydrophilic Interactions, Models, Molecular, Mutant Proteins, Protein Binding, Protein Conformation, Protein Domains, Protein Subunits, Receptors, Coronavirus, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Virus Internalization
Amino Acid Substitution, Angiotensin-Converting Enzyme 2, Antibodies, Viral, COVID-19, Cryoelectron Microscopy, Humans, Hydrophobic and Hydrophilic Interactions, Models, Molecular, Mutant Proteins, Protein Binding, Protein Conformation, Protein Domains, Protein Subunits, Receptors, Coronavirus, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Virus Internalization
Science
Date: Apr. 30, 2021
PubMed ID: 33727252
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