A Structural Analysis of Proteinaceous Nanotube Cavities and Their Applications in Nanotechnology.

Protein nanotubes offer unique properties to the materials science field that allow them to fulfill various functions in drug delivery, biosensors and energy storage. Protein nanotubes are chemically diverse, modular, biodegradable and nontoxic. Furthermore, although the initial design or repurposing of such nanotubes is highly complex, the field has matured to understand underlying chemical and physical properties to a point where applications are successfully being developed. An important feature of a nanotube is its ability to bind ligands via its internal cavities. As ligands of interest vary in size, shape and chemical properties, cavities have to be able to accommodate very specific features. As such, understanding cavities on a structural level is essential for their effective application. The objective of this review is to present the chemical and physical diversity of protein nanotube cavities and highlight their potential applications in materials science, specifically in biotechnology.

An ultra-stable redox-controlled self-assembling polypeptide nanotube for targeted imaging and therapy in cancer.

We introduce a self-assembling polypeptide-based nanotube system having the ability to specifically target cancer cells. The nanotubes target the cancer cell surface through integrin engagement with the help of multiple RGD units present along their surface. While the nanotubes are non-toxic towards cells in general, they can be loaded with suitable drugs to be released in a sustained manner in cancer cells. In addition, the nanotubes can be utilized for cellular imaging using any covalently tagged fluorescent dye. They are stable over a wide range of temperature due to intermolecular disulphide bonds formed during the self-assembly process. At the same time, presence of disulphide bonds provides a redox molecular switch for their degradation. Taken together this system provides a unique avenue for multimodal formulation in cancer therapy.

Switching between the alternative structures and functions of a 2-Cys peroxiredoxin, by site-directed mutagenesis.

Members of the typical 2-Cys peroxiredoxin (Prx) subfamily represent an intriguing example of protein moonlighting behavior since this enzyme shifts function: indeed, upon chemical stimuli, such as oxidative stress, Prx undergoes a switch from peroxidase to molecular chaperone, associated to a change in quaternary structure from dimers/decamers to higher-molecular-weight (HMW) species. In order to detail the structural mechanism of this switch at molecular level, we have designed and expressed mutants of peroxiredoxin I from Schistosoma mansoni (SmPrxI) with constitutive HMW assembly and molecular chaperone activity. By a combination of X-ray crystallography, transmission electron microscopy and functional experiments, we defined the structural events responsible for the moonlighting behavior of 2-Cys Prx and we demonstrated that acidification is coupled to local structural variations localized at the active site and a change in oligomerization to HMW forms, similar to those induced by oxidative stress. Moreover, we suggest that the binding site of the unfolded polypeptide is at least in part contributed by the hydrophobic surface exposed by the unfolding of the active site. We also find an inverse correlation between the extent of ring stacking and molecular chaperone activity that is explained assuming that the binding occurs at the extremities of the nanotube, and the longer the nanotube is, the lesser the ratio binding sites/molecular mass is.