Symmetry-Based Design and Structure of Self-Assembling Protein Cages and Nanomaterials

Abstract

Nature is replete with self-assembling molecular structures having diverse cellular functions. The largest and most sophisticated types are built from many copies of one protein molecule (or a few distinct protein molecules) arranged following principles of symmetry. Well-studied viral capsids and lesser-known bacterial microcompartments provide examples of natural closed shell architectures. A long-standing engineering goal has been to design novel protein molecules to self-assemble into geometrically specific structures similar to the extraordinary structures evolved in Nature. Practical routes to this goal have been developed by using ideas in symmetry to articulate the minimum design requirements for achieving various types of symmetric architectures, including cages, extended two-dimensional layers, and three-dimensional crystalline materials. The key requirement is generally that two distinct self-associating interfaces have to be built into the designed protein molecule, following specific geometric specifications. Recent experiments have demonstrated success using two alternate strategies, one based on fusing together two simple oligomers (e.g. a dimer and a trimer) in a geometrically specific orientation, and one based on designing one new interface into a natural oligomer (which already bears one interface). The success of these strategies has been proven by determining crystal structures of several giant, self-assembling protein cages (100-200 Å in diameter), created by design. The ability to create sophisticated supramolecular structures from designed protein subunits opens the way to broad applications in synthetic biology. Design principles and strategies will be discussed, along with current successes.