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TitleTransformation of a Viral Capsid from Nanocages to Nanotubes and Then to Hydrogels: Redirected Self-Assembly and Effects on Immunogenicity.
Journal, issue, pagesACS Nano, Vol. 18, Issue 21, Page 13755-13767, Year 2024
Publish dateMay 28, 2024
AuthorsMengsi Yang / Guibo Rao / Long Li / Linlin Qi / Chun Ma / Hui Zhang / Jun Gong / Bin Wei / Xian-En Zhang / Guosong Chen / Sheng Cao / Feng Li /
PubMed AbstractThe ability to manipulate the self-assembly of proteins is essential to understanding the mechanisms of life and beneficial to fabricating advanced nanomaterials. Here, we report the transformation ...The ability to manipulate the self-assembly of proteins is essential to understanding the mechanisms of life and beneficial to fabricating advanced nanomaterials. Here, we report the transformation of the MS2 phage capsid from nanocages to nanotubes and then to nanotube hydrogels through simple point mutations guided by interfacial interaction redesign. We demonstrate that site 70, which lies in the flexible FG loop of the capsid protein (CP), is a "magic" site that can largely dictate the final morphology of assemblies. By varying the amino acid at site 70, with the aid of a cysteine-to-alanine mutation at site 46, we achieved the assembly of double-helical or single-helical nanotubes in addition to nanocages. Furthermore, an additional cysteine substitution on the surface of nanotubes mediated their cross-linking to form hydrogels with reducing agent responsiveness. The hierarchical self-assembly system allowed for the investigation of morphology-related immunogenicity of MS2 CPs, which revealed dramatic differences among nanocages, nanotubes, and nanotube hydrogels in terms of immune response types, antibody levels and T cell functions. This study provides insights into the assembly manipulation of protein nanomaterials and the customized design of nanovaccines and drug delivery systems.
External linksACS Nano / PubMed:38752610
MethodsEM (helical sym.)
Resolution2.61 - 3.8 Å
Structure data

38892

8y3n

EMDB-38892, PDB-8y3n:
The self-assembled nanotube of CPC46A/Q70C
Method: EM (helical sym.) / Resolution: 3.8 Å

38898

8y3t

EMDB-38898, PDB-8y3t:
The self-assembled nanotube of CPC46A/Q70H
Method: EM (helical sym.) / Resolution: 2.61 Å

38900

8y3v

EMDB-38900, PDB-8y3v:
The self-assembled nanotube of CPC46A/Q70V
Method: EM (helical sym.) / Resolution: 3.46 Å

Source
  • emesvirus zinderi
KeywordsVIRAL PROTEIN / Capsid protein / Self-assembly / Nanotube

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