6XI6

Hierarchical design of multi-scale protein complexes by combinatorial assembly of oligomeric helical bundle and repeat protein building blocks

Summary for 6XI6

• Entry DOI: 10.2210/pdb6xi6/pdb
• Descriptor: helical fusion design (2 entities in total)
• Functional Keywords: helical fusion, de novo design, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 30783.76

Authors

Bera, A.K.,Hsia, Y.,Kang, A.S.,Shankaran, B.,Baker, D. (deposition date: 2020-06-19, release date: 2021-06-02, Last modification date: 2024-10-23)

Primary citation

Hsia, Y.,Mout, R.,Sheffler, W.,Edman, N.I.,Vulovic, I.,Park, Y.J.,Redler, R.L.,Bick, M.J.,Bera, A.K.,Courbet, A.,Kang, A.,Brunette, T.J.,Nattermann, U.,Tsai, E.,Saleem, A.,Chow, C.M.,Ekiert, D.,Bhabha, G.,Veesler, D.,Baker, D.
Design of multi-scale protein complexes by hierarchical building block fusion.
Nat Commun, 12:2294-2294, 2021

PubMed Abstract: A systematic and robust approach to generating complex protein nanomaterials would have broad utility. We develop a hierarchical approach to designing multi-component protein assemblies from two classes of modular building blocks: designed helical repeat proteins (DHRs) and helical bundle oligomers (HBs). We first rigidly fuse DHRs to HBs to generate a large library of oligomeric building blocks. We then generate assemblies with cyclic, dihedral, and point group symmetries from these building blocks using architecture guided rigid helical fusion with new software named WORMS. X-ray crystallography and cryo-electron microscopy characterization show that the hierarchical design approach can accurately generate a wide range of assemblies, including a 43 nm diameter icosahedral nanocage. The computational methods and building block sets described here provide a very general route to de novo designed protein nanomaterials.

PubMed: 33863889
DOI: 10.1038/s41467-021-22276-z

Experimental method

X-RAY DIFFRACTION (2.69 Å)