One ring (or two) to hold them all – on the structure and function of protein nanotubes

Abstract

Understanding the structural determinants relevant to the formation of supramolecular assemblies of homo‐oligomeric proteins is a traditional and central scope of structural biology. The knowledge thus gained is crucial both to infer their physiological function and to exploit their architecture for bionanomaterials design. Protein nanotubes made by one‐dimensional arrays of homo‐oligomers can be generated by either a commutative mechanism, yielding an ‘open’ structure (e.g. actin), or a noncommutative mechanism, whereby the final structure is formed by hierarchical self‐assembly of intermediate ‘closed’ structures. Examples of the latter process are poorly described and the rules by which they assemble have not been unequivocally defined. We have collected and investigated examples of homo‐oligomeric circular arrangements that form one‐dimensional filaments of stacked rings by the noncommutative mechanism in vivo and in vitro. Based on their quaternary structure, circular arrangements of protein subunits can be subdivided into two groups that we term Rings of Dimers (e.g. peroxiredoxin and stable protein 1) and Dimers of Rings (e.g. thermosome/rosettasome), depending on the sub‐structures that can be identified within the assembly (and, in some cases, populated in solution under selected experimental conditions). Structural analysis allowed us to identify the determinants by which ring‐like molecular chaperones form filamentous‐like assemblies and to formulate a novel hypothesis by which nanotube assembly, molecular chaperone activity and macromolecular crowding may be interconnected.

Identification of 2-Cys Peroxiredoxin (BmTPx-2) as Antioxidant Active Molecule from Babesia microti

“…Prxs are divided into three types based on the number and position of conserved cysteine residues, namely, 1-Cys, typical 2-Cys and 2-Cys type ( Rhee et al, 2001 ; Wood et al, 2003 ; Rhee, 2016 ). The functional unit of typical 2-Cys Prxs is a homodimer ( Angelucci et al, 2015 , 2016 ). However, the 2-Cys TPx-2 of B. microti has not been characterized to date.…”

Bio‐Assisted Tailored Synthesis of Plasmonic Silver Nanorings and Site‐Selective Deposition on Graphene Arrays

“…Ten identical subunits (≈25 kDa) of PRX, under reducing physiological conditions, associate into five dimers, which in turn undergo self‐assembly into a large and stable ring‐like complex (≈250 kDa) with thickness, and outer and inner diameters of 4.5, 12, and 6 nm, respectively (PDB code: 3ZTL) . Subunits interact in such a way that the PRX ring's bottom and top surfaces are identical thus providing a double‐faced appearance, while the inner and outer surfaces of the ring present distinct features that can be exploited for different protein derivatization …”

“…[44] Subunits interact in such a way that the PRX ring's bottom and top surfaces are identical thus providing a double-faced appearance, while the inner and outer surfaces of the ring present distinct features that can be exploited for different protein derivatization. [48] Here we present a bio-assisted synthesis of plasmonic silver nanorings using the ring-like protein PRX as a scaffold (Figure 1). Electron microscopy, absorbance, and energy dispersion spectroscopy show that the surface amino acids of PRX can bind and arrange Ag + ions in aqueous solution to allow seeding growth of Ag 0 under wet reducing conditions to finally achieve the synthesis of nanorings with inner and outer diameters down to 28 and 3 nm, respectively (PRX-AgNRs).…”

A peroxiredoxin-based proteinaceous scaffold for the growth and differentiation of neuronal cells and tumour stem cells in the absence of prodifferentiation agents

“…An attractive feature of these Prxs is the propensity of the protein toroid to associate into high‐molecular weight (HMW) complexes. Although the structural characterization of these HMW forms is sparse, the most reported assembly is a stack of toroid oligomers (Saccoccia et al , ; Angelucci et al , ; Phillips et al , ; Radjainia et al , ), but other more complex structures, including clusters and cages (Meissner et al , , Phillips et al , ), have been reported.…”

“…On these bases, the aims of this study were to create a protein scaffold using two different Prx mutants able to form protein nanotubes, smPrxI (C48S) from S. mansoni (Angelucci et al , ; Ardini et al , ) and peroxiredoxin III SP22 (C47S) from bovines (Gourlay et al , ), for the preparation of plates that enable the growth and differentiation of primary neurons, neuroblastoma cells and cancer stem cells from human and/or animal origin, using a common culture medium for mammalian cells, devoid of any prodifferentiation agent. The results obtained demonstrate that use of a nanotubular protein scaffold allows the growth and differentiation of neural cells, this phenomenon being directly linked to the oligomeric state of Prxs, since the use of wild‐type (WT) PrxI from Schistosoma mansoni does not induce the same effects.…”