The self-assembly of proteins into highly ordered nanoscale architectures is a hallmark of biological systems. The sophisticated functions of these molecular machines have inspired the development of methods to engineer self-assembling protein nanostructures; however, the design of multi-component protein nanomaterials with high accuracy remains an outstanding challenge. Here we report a computational method for designing protein nanomaterials in which multiple copies of two distinct subunits co-assemble into a specific architecture. We use the method to design five 24-subunit cage-like protein nanomaterials in two distinct symmetric architectures and experimentally demonstrate that their structures are in close agreement with the computational design models. The accuracy of the method and the number and variety of two-component materials that it makes accessible suggest a route to the construction of functional protein nanomaterials tailored to specific applications.
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Protein Data Bank
The crystal structures and structure factors for the designed materials have been deposited in the RCSB Protein Data Bank (http://www.rcsb.org/) under the accession codes 4NWN (T32-28), 4NWO (T33-15), 4NWP (T33-21, R32 crystal form), 4NWQ (T33-21, F4132 crystal form) and 4NWR (T33-28).
We thank D. Shi and B. Nannenga (JFRC) for help with electron microscopy, F. DiMaio and R. Moretti for assistance with software development, P. Greisen for scripts used to compare side-chain conformations, J. Gallaher for technical assistance, M. Collazo for help with preliminary crystallization screening, D. Cascio and M. Sawaya for help with crystallographic experiments, and M. Capel, J. Schuermann and I. Kourinov at NE-CAT beamline 24-ID-C for help with data collection. This work was supported by the Howard Hughes Medical Institute (T.G. and D.B.) and the JFRC visitor program (S.G.), the National Science Foundation under CHE-1332907 (D.B. and T.O.Y.), grants from the International AIDS Vaccine Initiative, DTRA (N00024-10-D-6318/0024), AFOSR (FA950-12-10112) and DOE (DE-SC0005155) to D.B., an NIH Biotechnology Training Program award to D.E.M. (T32GM067555) and an NSF graduate research fellowship to J.B.B. (DGE-0718124). T.O.Y. and D.E.M. also acknowledge support from the BER programme of the DOE Office of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding bodies.
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Nature Immunology (2018)