9UO6

Cryo-EM structure of the Xenopus IgX-Fc hexamer

Summary for 9UO6

• Entry DOI: 10.2210/pdb9uo6/pdb
• EMDB information: 64375
• Descriptor: Uncharacterized LOC101027262 precursor (1 entity in total)
• Functional Keywords: complex, polymeric antibody, immune system
• Biological source: Xenopus laevis (African clawed frog)
• Total number of polymer chains: 12
• Total formula weight: 286944.49

Authors

Ji, C.,Zhang, R.,Xiao, J. (deposition date: 2025-04-25, release date: 2025-12-17)

Primary citation

Zhang, R.,Ji, C.,Li, S.,Li, N.,Gao, N.,Xiao, J.
Xenopus IgX informs engineering strategies of IgM and IgG hexamers.
Sci Adv, 11:eaea3737-eaea3737, 2025

PubMed Abstract: Polymeric immunoglobulins are essential components of the immune system in jawed vertebrates. While mammalian immunoglobulin M (IgM) typically forms a pentamer linked by the joining chain (J-chain), IgX can assemble into a J-chain-independent polymer. Here, we present the cryo-electron microscopy (cryo-EM) structure of IgX, revealing its hexameric configuration. By incorporating the IgX tailpiece into human IgM, we achieved efficient IgM hexamer formation. Truncating IgM's natural tailpiece to a range of 11 to 16 residues also substantially enhanced hexamerization efficiency. Furthermore, introducing a shortened IgM tailpiece to IgG resulted in effective IgG hexamer formation. We further show that the engineered IgM and IgG hexamers targeting CD20 demonstrated robust complement-dependent cytotoxicity (CDC) against several B lymphoma cells. In addition, the IgG-Fc hexamer functioned as a decoy, attenuating CDC in cell cultures. These findings deepen our understanding of polymeric immunoglobulin evolution and introduce innovative strategies for the development of IgM- and IgG-based biologics.

PubMed: 41191733
DOI: 10.1126/sciadv.aea3737

Experimental method

ELECTRON MICROSCOPY (3.29 Å)