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TitleCryo-ET of IgG bivalent binding on SARS-CoV-2 provides structural basis for antibody avidity.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateApr 11, 2026
AuthorsHangping Yao / Yutong Song / Qi Huang / Miaojin Zhu / Jiaming Liang / Zheyuan Zhang / Xiaodi Zhang / Dongyang Dong / Danrong Shi / Zhigang Wu / Xiangyun Lu / Haibo Wu / Yong Chen / Sai Li /
PubMed AbstractThe bivalent nature of IgG antibodies can enhance its neutralization potency against enveloped viruses; however, on-virion structural details of IgG bivalent binding with antigens remain elusive. ...The bivalent nature of IgG antibodies can enhance its neutralization potency against enveloped viruses; however, on-virion structural details of IgG bivalent binding with antigens remain elusive. Here we investigate how two potent IgGs P17 and S309 interact with S-trimers on the SARS-CoV-2 surface by cryo-ET. We find both IgGs exploit the mobility of S-trimers to form diverse configurations of S-IgG dimer-of-trimers, which oligomerize into higher-order patterns. Specifically, P17 stabilizes S-trimers into linear assemblies within minutes, whereas S309 primarily stabilizes S-trimer into circular assemblies that extend into lattice-like structures. Both assembly patterns effectively activate complement cascade. Additionally, both IgGs can facilitate inter-virion coupling through bivalent binding of opposing S-trimers, potentially enhancing immune recognition and clearance. These findings establish a structural framework for understanding IgG avidity in neutralizing enveloped viruses and offer valuable insights for antibody engineering and vaccine design.
External linksNat Commun / PubMed:41965897 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution11.4 - 16.0 Å
Structure data

EMDB-66002: Subtomogram averaging of SARS-CoV-2 spike-P17-IgG Gemini structure
Method: EM (subtomogram averaging) / Resolution: 12.4 Å

EMDB-66003: Subtomogram averaging of SARS-CoV-2 spike-P17-IgG solo structure
Method: EM (subtomogram averaging) / Resolution: 11.4 Å

EMDB-66004: Subtomogram averaging of spike-P17-IgG solo structure on fixed SARS-CoV-2
Method: EM (subtomogram averaging) / Resolution: 11.4 Å

EMDB-66005: Subtomogram averaging of SARS-CoV-2 spike-S309-IgG Gemini structure
Method: EM (subtomogram averaging) / Resolution: 14.4 Å

EMDB-66006: Subtomogram averaging of SARS-CoV-2 spike-S309-IgG solo structure in 1-RBD-up conformation
Method: EM (subtomogram averaging) / Resolution: 14.5 Å

EMDB-66007: Subtomogram averaging of SARS-CoV-2 spike-S309-IgG solo structure in closed conformation
Method: EM (subtomogram averaging) / Resolution: 16.0 Å

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