EMD-22927

Single-particle
3.64 Å
EMD-22927 Deposition: 03/11/2020
Map released: 09/12/2020
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-22927

Cryo-EM structure of triple ACE2-bound SARS-CoV-2 trimer spike at pH 7.4

EMD-22927

Single-particle
3.64 Å
EMD-22927 Deposition: 03/11/2020
Map released: 09/12/2020
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Severe acute respiratory syndrome coronavirus 2, Homo sapiens
Sample: Triple ACE2-bound SARS-CoV-2 Trimer
Fitted models: 7kms (Avg. Q-score: 0.262)

Deposition Authors: Gorman J , Kwong PD
Cryo-EM Structures of SARS-CoV-2 Spike without and with ACE2 Reveal a pH-Dependent Switch to Mediate Endosomal Positioning of Receptor-Binding Domains.
PUBMED: 33271067
DOI: doi:10.1016/j.chom.2020.11.004
ISSN: 1934-6069
Abstract:
The SARS-CoV-2 spike employs mobile receptor-binding domains (RBDs) to engage the human ACE2 receptor and to facilitate virus entry, which can occur through low-pH-endosomal pathways. To understand how ACE2 binding and low pH affect spike conformation, we determined cryo-electron microscopy structures-at serological and endosomal pH-delineating spike recognition of up to three ACE2 molecules. RBDs freely adopted "up" conformations required for ACE2 interaction, primarily through RBD movement combined with smaller alterations in neighboring domains. In the absence of ACE2, single-RBD-up conformations dominated at pH 5.5, resolving into a solitary all-down conformation at lower pH. Notably, a pH-dependent refolding region (residues 824-858) at the spike-interdomain interface displayed dramatic structural rearrangements and mediated RBD positioning through coordinated movements of the entire trimer apex. These structures provide a foundation for understanding prefusion-spike mechanics governing endosomal entry; we suggest that the low pH all-down conformation potentially facilitates immune evasion from RBD-up binding antibody.