12JZ

Cryo-EM structure of SARS-CoV-2 BA.3.2.1 Spike with K852A mutation, closed conformation

Summary for 12JZ

• Entry DOI: 10.2210/pdb12jz/pdb
• EMDB information: 76501
• Descriptor: SARS-CoV-2 BA.3.2.1 spike with K852A mutation, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: sars-cov-2, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 3
• Total formula weight: 433303.43

Authors

Wang, Y.,Hu, Y.,Xie, X. (deposition date: 2026-04-08, release date: 2026-06-17, Last modification date: 2026-08-19)

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 (2.35 Å)