| Autor: |
Yang Hsia, Rubul Mout, William Sheffler, Natasha I. Edman, Ivan Vulovic, Young-Jun Park, Rachel L. Redler, Matthew J. Bick, Asim K. Bera, Alexis Courbet, Alex Kang, TJ Brunette, Una Nattermann, Evelyn Tsai, Ayesha Saleem, Cameron M. Chow, Damian Ekiert, Gira Bhabha, David Veesler, David Baker |
| Rok vydání: |
2020 |
| Popis: |
A goal of de novo protein design is to develop a systematic and robust approach to generating complex nanomaterials from stable building blocks. Due to their structural regularity and simplicity, a wide range of monomeric repeat proteins and oligomeric helical bundle structures have been designed and characterized. Here we describe a stepwise hierarchical approach to building up multi-component symmetric protein assemblies using these structures. We first connect designed helical repeat proteins (DHRs) to designed helical bundle proteins (HBs) to generate a large library of heterodimeric and homooligomeric building blocks; the latter have cyclic symmetries ranging from C2 to C6. All of the building blocks have repeat proteins with accessible termini, which we take advantage of in a second round of architecture guided rigid helical fusion (WORMS) to generate larger symmetric assemblies including C3 and C5 cyclic and D2 dihedral rings, a tetrahedral cage, and a 120 subunit icosahedral cage. Characterization of the structures by small angle x-ray scattering, x-ray crystallography, and cryo-electron microscopy demonstrates that the hierarchical design approach can accurately and robustly generate a wide range of macromolecular assemblies; with a diameter of 43nm, the icosahedral nanocage is the largest structurally validated designed cage to date. The computational methods and building block sets described here provide a very general route to new de novo designed symmetric protein nanomaterials. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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