Significance The spike proteins of most current severe acute respiratory syndrome coronavirus 2 isolates contain a D614G substitution, by comparison with the spike protein of initial isolates. In this study we present high-resolution, single-particle cryo-electron microscopy structures of the G614 spike variant showing that it adopts a predominantly open conformation, unlike the D614 spike that is mostly closed. We conclude that the D614G substitution promotes “opening” of the spike, priming it for binding to the receptor ACE2 and possibly for its subsequent role in membrane fusion. The observed open conformation of the G614 spike may be the reason for the current virus’ reported increased infectivity and its current predominance. The majority of currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses have mutant spike glycoproteins that contain the D614G substitution. Several studies have suggested that spikes with this substitution are associated with higher virus infectivity. We use cryo-electron microscopy to compare G614 and D614 spikes and show that the G614 mutant spike adopts a range of more open conformations that may facilitate binding to the SARS-CoV-2 receptor, ACE2, and the subsequent structural rearrangements required for viral membrane fusion.
【저자키워드】 SARS-CoV-2, coronavirus, spike, D614G, cryo-EM, 【초록키워드】 viruses, Structure, ACE2, coronavirus, variant, spike glycoprotein, Cryo-electron microscopy, severe acute respiratory syndrome Coronavirus, SARS-CoV-2 receptor, Spike protein, electron microscopy, Viral, spike glycoproteins, membrane fusion, mutant, receptor, respiratory, binding, Spike proteins, opening, isolates, High-resolution, structural rearrangement, reason for, open, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, spikes, viral membrane, conformation, priming, reason, circulating, receptor ACE2, virus infectivity, D614G substitution, cryo, isolate, initial, virus, reported, subsequent, required, facilitate, majority, the spike protein, suggested, promote, Significance, the SARS-CoV-2, 【제목키워드】 spike glycoprotein,