Precisely patterned nanofibres made from extendable protein multiplexes

Neville P Bethel; Andrew J Borst; Fabio Parmeggiani; Matthew J Bick; T J Brunette; Hannah Nguyen; Alex Kang; Asim K Bera; Lauren Carter; Marcos C Miranda; Ryan D Kibler; Mila Lamb; Xinting Li; Banumathi Sankaran; David Baker

doi:10.1038/s41557-023-01314-x

Precisely patterned nanofibres made from extendable protein multiplexes

Nat Chem. 2023 Dec;15(12):1664-1671. doi: 10.1038/s41557-023-01314-x. Epub 2023 Sep 4.

Authors

Neville P Bethel^{1

2

3}, Andrew J Borst^{1

2}, Fabio Parmeggiani^{4

5

6}, Matthew J Bick^{1

2}, T J Brunette^{1

2}, Hannah Nguyen^{1

2}, Alex Kang^{1

2}, Asim K Bera^{1

2}, Lauren Carter^{1

2}, Marcos C Miranda^{1

2}, Ryan D Kibler^{1

2}, Mila Lamb^{1

2}, Xinting Li^{1

2}, Banumathi Sankaran⁷, David Baker^{8

9

10}

Affiliations

¹ Department of Biochemistry, University of Washington, Seattle, WA, USA.
² Institute for Protein Design, University of Washington, Seattle, WA, USA.
³ Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
⁴ School of Chemistry, University of Bristol, Bristol, UK.
⁵ School of Biochemistry, University of Bristol, Bristol, UK.
⁶ Bristol Biodesign Institute, University of Bristol, Bristol, UK.
⁷ Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, CA, USA.
⁸ Department of Biochemistry, University of Washington, Seattle, WA, USA. dabaker@uw.edu.
⁹ Institute for Protein Design, University of Washington, Seattle, WA, USA. dabaker@uw.edu.
¹⁰ Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA. dabaker@uw.edu.

Abstract

Molecular systems with coincident cyclic and superhelical symmetry axes have considerable advantages for materials design as they can be readily lengthened or shortened by changing the length of the constituent monomers. Among proteins, alpha-helical coiled coils have such symmetric, extendable architectures, but are limited by the relatively fixed geometry and flexibility of the helical protomers. Here we describe a systematic approach to generating modular and rigid repeat protein oligomers with coincident C₂ to C₈ and superhelical symmetry axes that can be readily extended by repeat propagation. From these building blocks, we demonstrate that a wide range of unbounded fibres can be systematically designed by introducing hydrophilic surface patches that force staggering of the monomers; the geometry of such fibres can be precisely tuned by varying the number of repeat units in the monomer and the placement of the hydrophilic patches.

Precisely patterned nanofibres made from extendable protein multiplexes

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