9YSS

Local refinement of hACE2/SARS-CoV-2 LP.8.1 spike, conformation 1

Summary for 9YSS

• Entry DOI: 10.2210/pdb9yss/pdb
• Related: 9YSJ 9YSK 9YSR
• EMDB information: 73393 73394 73395 73396 73404 73405 73408 73409 73426 73427 73428 73429
• Descriptor: Angiotensin-converting enzyme 2, SARS-CoV-2 LP.8.1 spike, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sars-cov-2, viral protein, viral protein-hydrolase complex, viral protein/hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 215893.12

Authors

Wang, Y.,Hu, Y.,Chen, Z.,Liang, B.,Xie, X. (deposition date: 2025-10-19, release date: 2026-06-17, Last modification date: 2026-09-30)

Primary citation

Wang, Y.,Hu, Y.,Chen, Z.,Zou, J.,Zhang, K.,Ren, P.,Shi, P.Y.,Liang, B.,Xie, X.
Functional and structural basis of Omicron BA.3.2.1 spike.
Cell Rep, 45:117812-117812, 2026

PubMed Abstract: SARS-CoV-2 BA.3.2 sublineages, derived from BA.3 and carrying substantial spike divergence, raised concerns about altered fitness and antigenicity. Using BA.3.2.1 as a representative strain, we engineered live-attenuated SARS-CoV-2 encoding BA.3.2.1, LP.8.1, or XEC spikes and benchmarked them against BA.3 and KP.3. BA.3.2.1 outcompetes BA.3 in primary human airway epithelium but replicates less efficiently than JN.1 descendants and shows the greatest resistance to neutralization by KP.2/KP.3 convalescent sera. Although BA.3.2.1 RBD binds hACE2 with high affinity, its trimeric spike engages hACE2 less efficiently than LP.8.1. Cryoelectron microscopy structures reveal that BA.3.2.1 spike predominantly adopts a compact, asymmetric closed conformation stabilized by protomer rearrangements, N-linked glycosylation, and a distinct fusion-peptide-proximal region. This architecture increases spike stability, limits receptor engagement, reduces fusogenicity, and masks antibody-sensitive epitopes. Thus, BA.3.2.1 enhances immune evasion at the cost of replication fitness, providing a structural-functional explanation for BA.3.2's limited prevalence and underscoring the need for continued variant surveillance.

PubMed: 42571698
DOI: 10.1016/j.celrep.2026.117812

Experimental method

ELECTRON MICROSCOPY (3.67 Å)