7W9F

SARS-CoV-2 Delta S-RBD-8D3

Summary for 7W9F

• Entry DOI: 10.2210/pdb7w9f/pdb
• EMDB information: 32366
• Descriptor: The heavy chain of 8D3, The light chain of 8D3, Spike protein S1 (3 entities in total)
• Functional Keywords: sars-cov-2 delta variant spike protein, viral protein
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 94691.60

Authors

Cong, Y.,Liu, C.X. (deposition date: 2021-12-09, release date: 2022-01-12, Last modification date: 2024-11-13)

Primary citation

Wang, Y.,Liu, C.,Zhang, C.,Wang, Y.,Hong, Q.,Xu, S.,Li, Z.,Yang, Y.,Huang, Z.,Cong, Y.
Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies.
Nat Commun, 13:871-871, 2022

PubMed Abstract: The SARS-CoV-2 Delta variant is currently the dominant circulating strain in the world. Uncovering the structural basis of the enhanced transmission and altered immune sensitivity of Delta is particularly important. Here we present cryo-EM structures revealing two conformational states of Delta spike and S/ACE2 complex in four states. Our cryo-EM analysis suggests that RBD destabilizations lead to population shift towards the more RBD-up and S1 destabilized fusion-prone state, beneficial for engagement with ACE2 and shedding of S1. Noteworthy, we find the Delta T478K substitution plays a vital role in stabilizing and reshaping the RBM loop, enhancing interaction with ACE2. Collectively, increased propensity for more RBD-up states and the affinity-enhancing T478K substitution together contribute to increased ACE2 binding, providing structural basis of rapid spread of Delta. Moreover, we identify a previously generated MAb 8D3 as a cross-variant broadly neutralizing antibody and reveal that 8D3 binding induces a large K478 side-chain orientation change, suggesting 8D3 may use an "induced-fit" mechanism to tolerate Delta T478K mutation. We also find that all five RBD-targeting MAbs tested remain effective on Delta, suggesting that Delta well preserves the neutralizing antigenic landscape in RBD. Our findings shed new lights on the pathogenicity and antibody neutralization of Delta.

PubMed: 35169135
DOI: 10.1038/s41467-022-28528-w

Experimental method

ELECTRON MICROSCOPY (3.6 Å)