Blueprinting extendable nanomaterials with standardized protein blocks

Timothy F. Huddy, Yang Hsia, Ryan D. Kibler, Jinwei Xu, Neville Bethel, Deepesh Nagarajan, Rachel Redler, Philip J. Y. Leung, Connor Weidle, Alexis Courbet, Erin C. Yang, Asim K. Bera, Nicolas Coudray, S. John Calise, Fatima A. Davila-Hernandez, Hannah L. Han, Kenneth D. Carr, Zhe Li, Ryan McHugh, Gabriella Reggiano, Alex Kang, Banumathi Sankaran, Miles S. Dickinson, Brian Coventry, T. J. Brunette, Yulai Liu, Justas Dauparas, Andrew J. Borst, Damian Ekiert, Justin M. Kollman, Gira Bhabha and David Baker ()
Additional contact information
Timothy F. Huddy: University of Washington
Yang Hsia: University of Washington
Ryan D. Kibler: University of Washington
Jinwei Xu: University of Washington
Neville Bethel: University of Washington
Deepesh Nagarajan: M.S. Ramaiah University of Applied Sciences
Rachel Redler: NYU School of Medicine
Philip J. Y. Leung: University of Washington
Connor Weidle: University of Washington
Alexis Courbet: University of Washington
Erin C. Yang: University of Washington
Asim K. Bera: University of Washington
Nicolas Coudray: NYU School of Medicine
S. John Calise: University of Washington
Fatima A. Davila-Hernandez: University of Washington
Hannah L. Han: University of Washington
Kenneth D. Carr: University of Washington
Zhe Li: University of Washington
Ryan McHugh: University of Washington
Gabriella Reggiano: University of Washington
Alex Kang: University of Washington
Banumathi Sankaran: Lawrence Berkeley National Laboratory
Miles S. Dickinson: University of Washington
Brian Coventry: University of Washington
T. J. Brunette: University of Washington
Yulai Liu: University of Washington
Justas Dauparas: University of Washington
Andrew J. Borst: University of Washington
Damian Ekiert: NYU School of Medicine
Justin M. Kollman: University of Washington
Gira Bhabha: NYU School of Medicine
David Baker: University of Washington

Nature, 2024, vol. 627, issue 8005, 898-904

Abstract: Abstract A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies, in comparison, has been much more complex, largely owing to the irregular shapes of protein structures1. Here we describe extendable linear, curved and angled protein building blocks, as well as inter-block interactions, that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight ‘train track’ assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence–structure relationships, it has not previously been possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank three-dimensional canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to ‘back of an envelope’ architectural blueprints.

Date: 2024
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DOI: 10.1038/s41586-024-07188-4

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