Flexible spikes The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein enables viral entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor and is a major target for neutralizing antibodies. About 20 to 40 spikes decorate the surface of virions. Turoňová et al. now show that the spike is flexibly connected to the viral surface by three hinges that are well protected by glycosylation sites. The flexibility imparted by these hinges may explain how multiple spikes act in concert to engage onto the flat surface of a host cell. Science , this issue p. 203 Flexible hinges shielded by glycans in the coronavirus spike protein may allow scanning of the host cell surface. The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo–electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed prefusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and potentially to the development of safe vaccines.
【초록키워드】 SARS-CoV-2, ACE2, Vaccine development, coronavirus, Vaccines, Neutralizing antibodies, glycosylation, spike, antibody, SARS-COV-2 infection, tomography, angiotensin-converting enzyme 2, viral entry, Spike protein, Molecular dynamics simulation, coronavirus spike protein, receptor, glycan, binding, Safe, host cell, Science, acute respiratory syndrome, viral surface, domain, cell entry, virions, prefusion conformation, host cell surface, occurred, required, contribute, explain, glycosylated, engage, flat, 【제목키워드】 SARS-CoV-2 spike, Structural analysis, reveal,