GoKawiilWe thank D. Juergens for their help with computational design and scripts; F. Praetorius and D. Sahtoe for contributing de-novo-designed LHD heterodimer building blocks; Q. Dowling and W. Sheffler for helpful discussions; S. Gerben for their assistance with protein purification; N. Bethel for their assistance with molecular dynamics simulations; Y. Hsia for their assistance with field flow fractionation; and S. Dickinson and J. Quipse for their help with maintaining and operating the electron microscopes. Molecular graphics and cage models were generated with UCSF ChimeraX. This work was supported by the Defense Threat Reduction Agency (grant no. HDTRA1-19-1-0003 to S.W.) and the Burroughs Wellcome Fund (S.W.); The Audacious Project at the Institute for Protein Design (S.W., A.F., A.J.B., A.B., J.D., A.K., D.B.); a gift from Microsoft (D.C.); the National Science Foundation (grant no. CHE-2226466 to F.D.); the Human Frontiers Science Program (grant no. RGP0061/2019 to F.D.); the Bill and Melinda Gates Foundation (grant no. INV-043758 to C.W., J.D., A.K., A.B. and no. OPP1156262 to A.J.B.); the Howard Hughes Medical Institute (C.W., A.B., A.J.B., D.B.); the National Institutes of Health’s National Institute on Aging (grant no. R01AG063845 to A.B., A.F. A.J.B. and B.H.); Spark Therapeutics/Computational Design of a Half Size Functional (grant no. ABCA4 to K.W.); and The Nordstrom Barrier Institute for Protein Design Directors Fund (B.H.). Crystallographic work was done at the National Synchrotron Light Source II on beamline FMX (17-ID-2). The Center for Bio-Molecular Structure (CBMS) is primarily supported by the NIH-NIGMS through a Center Core P30 Grant (grant no. P30GM133893), and by the DOE Office of Biological and Environmental Research (grant no. KP1607011). NSLS-II is a US DOE Office of Science User Facility (operated under contract no. DE-SC0012704). This publication resulted from data collected using the beamtime obtained through NECAT BAG proposal no. 311950. L.J.H. was funded by NIH (grant nos. R01 GM132447 and R37 CA240765) the NIH Director’s Transformative Research Award (no. TR01 NS127186), a Hypothesis Fund Award and a Research Grant from HFSP (grant no. RGP0016/2022).
De novo design of quasisymmetric two-component protein cages
Why This Matters
The de novo design of quasisymmetric two-component protein cages represents a significant advancement in protein engineering, enabling the creation of highly specific and customizable nanostructures. This innovation has the potential to impact drug delivery, vaccine development, and nanotechnology by providing new platforms for precise molecular assembly. As a pioneering approach, it paves the way for more sophisticated and functional biomolecular materials in the tech industry and healthcare sectors.
Key Takeaways
- Enables the creation of customizable protein nanostructures with precise symmetry.
- Combines computational design and experimental validation for robust assembly.
- Opens new avenues for applications in drug delivery, vaccines, and nanotechnology.
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