Assembly of Multicomponent Protein Filaments Using Engineered Subunit Interfaces

ACS Synthetic Biology
Dominic J GloverDouglas S Clark

Abstract

Exploiting the ability of proteins to self-assemble into architectural templates may provide novel routes for the positioning of functional molecules in nanotechnology. Here we report the engineering of multicomponent protein templates composed of distinct monomers that assemble in repeating orders into a dynamic functional structure. This was achieved by redesigning the protein-protein interfaces of a molecular chaperone with helical sequences to create unique subunits that assemble through orthogonal coiled-coils into filaments up to several hundred nanometers in length. Subsequently, it was demonstrated that functional proteins could be fused to the subunits to achieve ordered alignment along filaments. Importantly, the multicomponent filaments had molecular chaperone activity and could prevent other proteins from thermal-induced aggregation, a potentially useful property for the scaffolding of enzymes. The design in this work is presented as proof-of-concept for the creation of modular templates that could potentially be used to position functional molecules, stabilize other proteins such as enzymes, and enable controlled assembly of nanostructures with unique topologies.

References

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Citations

Apr 3, 2020·Chemical Communications : Chem Comm·Samuel LimDouglas S Clark
Aug 21, 2020·Trends in Biotechnology·Joshua B McCluskeyDominic J Glover
Jul 24, 2020·ACS Synthetic Biology·Daniel L WinterDominic J Glover

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