Report

Accurate design of megadalton-scale two-component icosahedral protein complexes

See allHide authors and affiliations

Science  22 Jul 2016:
Vol. 353, Issue 6297, pp. 389-394
DOI: 10.1126/science.aaf8818

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Designed to assemble

Symmetric macromolecular structures that form cages, such as viral capsids, have inspired protein engineering. Bale et al. used pairwise combinations of dimeric, trimeric, or pentameric building blocks to design two-component, 120-subunit protein complexes with three distinct icosahedral architectures. The capsid-like nanostructures are large enough to hold nucleic acids or other proteins, and because they have two components, the assembly of cargoes such as drugs and vaccines can be done in a controlled way.

Science, this issue p. 389

Abstract

Nature provides many examples of self- and co-assembling protein-based molecular machines, including icosahedral protein cages that serve as scaffolds, enzymes, and compartments for essential biochemical reactions and icosahedral virus capsids, which encapsidate and protect viral genomes and mediate entry into host cells. Inspired by these natural materials, we report the computational design and experimental characterization of co-assembling, two-component, 120-subunit icosahedral protein nanostructures with molecular weights (1.8 to 2.8 megadaltons) and dimensions (24 to 40 nanometers in diameter) comparable to those of small viral capsids. Electron microscopy, small-angle x-ray scattering, and x-ray crystallography show that 10 designs spanning three distinct icosahedral architectures form materials closely matching the design models. In vitro assembly of icosahedral complexes from independently purified components occurs rapidly, at rates comparable to those of viral capsids, and enables controlled packaging of molecular cargo through charge complementarity. The ability to design megadalton-scale materials with atomic-level accuracy and controllable assembly opens the door to a new generation of genetically programmable protein-based molecular machines.

View Full Text