Design of multi-scale protein complexes by hierarchical building block fusion View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-04-16

AUTHORS

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, T. J. Brunette, Una Nattermann, Evelyn Tsai, Ayesha Saleem, Cameron M. Chow, Damian Ekiert, Gira Bhabha, David Veesler, David Baker

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. More... »

PAGES

2294

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-021-22276-z

DOI

http://dx.doi.org/10.1038/s41467-021-22276-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1137252140

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33863889


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