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TitleFour-component protein nanocages designed by programmed symmetry breaking.
Journal, issue, pagesNature, Vol. 638, Issue 8050, Page 546-552, Year 2025
Publish dateDec 18, 2024
AuthorsSangmin Lee / Ryan D Kibler / Green Ahn / Yang Hsia / Andrew J Borst / Annika Philomin / Madison A Kennedy / Buwei Huang / Barry Stoddard / David Baker /
PubMed AbstractFour, eight or twenty C3 symmetric protein trimers can be arranged with tetrahedral, octahedral or icosahedral point group symmetry to generate closed cage-like structures. Viruses access more ...Four, eight or twenty C3 symmetric protein trimers can be arranged with tetrahedral, octahedral or icosahedral point group symmetry to generate closed cage-like structures. Viruses access more complex higher triangulation number icosahedral architectures by breaking perfect point group symmetry, but nature appears not to have explored similar symmetry breaking for tetrahedral or octahedral symmetries. Here we describe a general design strategy for building higher triangulation number architectures starting from regular polyhedra through pseudosymmetrization of trimeric building blocks. Electron microscopy confirms the structures of T = 4 cages with 48 (tetrahedral), 96 (octahedral) and 240 (icosahedral) subunits, each with 4 distinct chains and 6 different protein-protein interfaces, and diameters of 33 nm, 43 nm and 75 nm, respectively. Higher triangulation number viruses possess very sophisticated functionalities; our general route to higher triangulation number nanocages should similarly enable a next generation of multiple antigen-displaying vaccine candidates and targeted delivery vehicles.
External linksNature / PubMed:39695226 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution4.5 - 6.87 Å
Structure data

EMDB-40267: CryoEM map of a T=1 off-target state of design Ico(T=4)-4
Method: EM (single particle) / Resolution: 6.54 Å

EMDB-40268: CryoEM map of a de novo designed T=4 octahedral nanocage hierarchically built from pseudosymmetric trimers; design Oct(T=4)-3
Method: EM (single particle) / Resolution: 6.87 Å

EMDB-40269: CryoEM map of a T=1 off-target state of design Oct(T=4)-3
Method: EM (single particle) / Resolution: 6.87 Å

PDB-8flx:
De novo designed homotrimer; the fusion product of BGL17 and DHR59
Method: X-RAY DIFFRACTION / Resolution: 4.5 Å

Source
  • synthetic construct (others)
KeywordsDE NOVO PROTEIN / de novo / computationally designed / designed / tandem repeat protein / kibloid / homotrimer

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