What is it about?

We're excited to announce that our latest research has been published in ACS Nano! Hollow protein particles are useful for delivery and catalysis. By studying how these proteins form and change their shapes, we can design them with specific properties. We discovered that a modified version of a protein, Aquifex aeolicus lumazine synthase (cpAaLS), forms different hollow structures (spherical and tubular). By controlling the changes in salt concentration and pH of the solution, we can control which shape forms. Using cryogenic electron microscopy, we found these structures are made of five-subunit units, and the shift from cage to tube happens due to the interaction of specific symmetries and the twist in the protein parts. Mathematical models suggest that these subunit arrangements create the most efficient patterns, and different shapes could be made by adjusting the angles between the units. These findings help guide the design of protein-based nanostructures with tailored shapes and properties.

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Why is it important?

We successfully controlled the assembly and structure of a circularly permuted cage-forming protein, revealing the molecular reason behind its flexible, shape-shifting nature. A short peptide, altered by a topological change, prevents certain symmetry interactions and holds the building blocks at specific angles, transforming the protein from a dodecahedron into a new helical structure. Another variant of this protein, NC-4, forms a mix of pentamers and hexamers, showing the protein's ability to adopt different shapes. This highlights the potential of circular permutation to modify or create custom protein cages. The patterns observed in the tubular structures represent the best possible arrangement for this specific protein, but other shapes are also possible, indicating the potential for new protein assemblies. The mathematical methods used in this study, like AngelaR and lattice models, can help predict unknown protein structures. Protein tubes are common in nature, playing roles in things like virus protection, bacterial movement, and cell shape. These biological examples inspire the creation of customisable protein tubes for applications in drug delivery, catalysis, and nanomaterials. The cpAaLS protein tubes, being modular and easily adjusted, offer a promising platform for designing biomimetic nanodevices. Our findings provide key insights for designing protein nanotubes with tailored shapes and behaviours.

Perspectives

It was great to contribute towards this fantastic work led by Yusuke Azum and his team at Jagiellonian University. Thanks also to the other partners at University of Leeds, and the University of York who all contributed to the successful result in our research at the nano level.

Professor Jonathan Gardiner Heddle
Durham University

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This page is a summary of: Dynamic Assembly of Pentamer-Based Protein Nanotubes, ACS Nano, February 2025, American Chemical Society (ACS),
DOI: 10.1021/acsnano.4c16192.
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