Design of multi-scale protein complexes by hierarchical building block fusion.

Autor: Hsia Y; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Biological Physics, Structure and Design Graduate Program, University of Washington, Seattle, WA, USA., Mout R; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Sheffler W; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Edman NI; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA, USA.; Medical Scientist Training Program, University of Washington, Seattle, WA, USA., Vulovic I; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Molecular Engineering Graduate Program, University of Washington, Seattle, WA, USA., Park YJ; Department of Biochemistry, University of Washington, Seattle, WA, USA., Redler RL; Department of Cell Biology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA., Bick MJ; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Bera AK; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Courbet A; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Kang A; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Brunette TJ; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Nattermann U; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Biological Physics, Structure and Design Graduate Program, University of Washington, Seattle, WA, USA., Tsai E; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Saleem A; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Chow CM; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Ekiert D; Department of Cell Biology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA.; Department of Microbiology, New York University School of Medicine, New York, NY, USA., Bhabha G; Department of Cell Biology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA., Veesler D; Department of Biochemistry, University of Washington, Seattle, WA, USA., Baker D; Department of Biochemistry, University of Washington, Seattle, WA, USA. dabaker@uw.edu.; Institute for Protein Design, University of Washington, Seattle, WA, USA. dabaker@uw.edu.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA. dabaker@uw.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Apr 16; Vol. 12 (1), pp. 2294. Date of Electronic Publication: 2021 Apr 16.
DOI: 10.1038/s41467-021-22276-z
Abstrakt: 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.
Databáze: MEDLINE