Dynamic Assembly of Pentamer-Based Protein Nanotubes.

Abstract

Hollow proteinaceous particles are useful nanometric containers for delivery and catalysis. Understanding the molecular mechanisms and the geometrical theory behind the polymorphic protein assemblies provides a basis for designing ones with the desired morphology. As such, we found that a circularly permuted variant of a cage-forming enzyme, <i>Aquifex aeolicus</i> lumazine synthase, cpAaLS, assembles into a variety of hollow spherical and cylindrical structures in response to changes in ionic strength. Cryogenic electron microscopy revealed that these structures are composed entirely of pentameric subunits, and the dramatic cage-to-tube transformation is attributed to the moderately hindered 3-fold symmetry interaction and the imparted torsion angle of the building blocks, where both mechanisms are mediated by an α-helix domain that is untethered from the native position by circular permutation. Mathematical modeling suggests that the unique double- and triple-stranded helical arrangements of subunits are optimal tiling patterns, while different geometries should be possible by modulating the interaction angles of the pentagons. These structural insights into dynamic, pentamer-based protein cages and nanotubes afford guidelines for designing nanoarchitectures with customized morphology and assembly characteristics.