Cryo-Electron Microscopy Structure of Human Peroxiredoxin-3 Filament Reveals the Assembly of a Putative Chaperone

Radjainia, Mazdak; Venugopal, Hariprasad; Desfosses, Ambroise; Phillips, Amy; Yewdall, N. Amy; Hampton, Mark B.; Gerrard, Juliet A.; Mitra, Alok K.

doi:10.1016/j.str.2015.03.019

Cited by 31 publications

(40 citation statements)

References 36 publications

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“…Peroxiredoxin (Prx) is a family of peroxidases that decomposes H 2 O 2 by employing cysteine as a catalytic site . The quaternary structures of Prxs are highly diverse: they can assemble into a homodimer, octamer, decamer, or dodecamer, and can further assemble into even higher molecular‐weight forms . These structural varieties of Prxs make them noteworthy targets in studies on protein assembly.…”

Section: Introductionmentioning

confidence: 99%

Disassembly of the ring‐type decameric structure of peroxiredoxin from Aeropyrum pernix K1 by amino acid mutation

Himiyama

Nakamura

2020

Protein Science

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The quaternary structure of peroxiredoxin from Aeropyrum pernix K1 (ApPrx) is a decamer, in which five homodimers are assembled in a pentagonal ring through hydrophobic interactions. In this study, we determined the amino acid (AA) residues of ApPrx crucial for forming the decamer using AA mutations. The ApPrx0Cys mutant, wherein all cysteine residues were mutated to serine, was prepared as a model protein to remove the influence of the redox states of the cysteines on its assembling behavior. The boundary between each homodimer of ApPrx0Cys contains characteristic aromatic AA residues forming hydrophobic interactions: F46, F80, W88, W210, and W211. We found that a single mutation of F46, F80, or W210 to alanine completely disassembled the ApPrx0Cys decamer to homodimers, which was clarified by gel-filtration chromatography and dynamic light scattering measurements. F46A, F80A, and W210A mutants lacked only one aromatic ring compared with ApPrx0Cys, indicating that the assembly is very sensitive to the surface structure of the protein. X-ray structures revealed two mechanisms of disassembly of the ApPrx decamer: loss of hydrophobicity between homodimers and flip of the arm domain. The AA residues targeted in this study are well conserved in ring-type Prx proteins, suggesting the importance of these residues in the assembly. This study demonstrates the sensitivity and modifiability of peroxiredoxin assembly by a simple AA mutation. K E Y W O R D Salanine substitution, hydrophobic interaction, peroxiredoxin, protein assembly

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Section: Introductionmentioning

confidence: 99%

Disassembly of the ring‐type decameric structure of peroxiredoxin from Aeropyrum pernix K1 by amino acid mutation

Himiyama

Nakamura

2020

Protein Science

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“…15 pH changes have an apparent effect on the oligomeric state of peroxiredoxin, 15 with wild type HsPrx3 assembling into 1D tubes at pH 4.0. 28 In the current work, we first assessed optimal conditions for the formation of high molecular weight (HMW) species of the tagged human peroxiredoxin III (HsPrx3-6his) using analytical ultracentrifugation (AUC) and transmission electron microscopy (TEM). The inclusion of a tag (which locates to the center of the dodecameric ring) also provides a convenient method for metal binding through chelation to the six histidine residues.…”

Section: Introductionmentioning

confidence: 99%

Formation of supramolecular protein structures on gold surfaces

et al. 2017

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Recent research has highlighted the exciting possibilities enabled by the use of protein structures as nanocomponents to form functional nanodevices. To this end, control over protein-protein and protein-surface interactions is essential. In this study, the authors probe the interaction of human peroxiredoxin 3 with gold surfaces, a protein that has been previously identified as having potential use in nanotechnology. Analytical ultracentrifugation and transmission electron microscopy revealed the pH mediated assembly of protein toroids into tubular structures across a small pH range. Quartz crystal microbalance with dissipation measurements showed differences in absorbed protein mass when pH is switched from pH 8.0 to 7.2, in line with the formation of supramolecular structures observed in solution studies. Scanning tunneling microscopy under ambient conditions showed that these protein tubes form on surfaces in a concentration dependent manner, with a tendency for protein adsorption and supramolecular assembly at the edges of Au(111) terraces. Finally, self-assembled monolayer modification of Au surfaces was explored as a means to control the adsorption and orientation of pH triggered protein structures.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Cimini

Ardini

Gentile

et al. 2016

J Tissue Eng Regen Med

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The use of nanoscale materials in the design of scaffolds for CNS tissue is increasing, due to their ability to promote cell adhesion, to mimic an extracellular matrix microenvironment and to interact with neuronal membranes. In this framework, one of the major challenges when using undifferentiated neural cells is how to control the differentiation process. Here we report the characterization of a scaffold based on the self-assembled nanotubes of a mutant of the protein peroxiredoxin (from Schistosoma mansoni or Bos taurus), which allows the growth and differentiation of a model neuronal cell line (SHSY5Y). The results obtained demonstrate that SHSY5Y cells grow without any sign of toxicity and develop a neuronal phenotype, as shown by the expression of neuronal differentiation markers, without the use of any differentiation supplement, even in the presence of serum. The prodifferentiation effect is demonstrated to be dependent on the formation of the protein nanotube, since a wild-type (WT) form of the peroxiredoxin from Schistosoma mansoni does not induce any differentiation. The protein scaffold was also able to induce the spread of glioblastoma cancer stem cells growing in neurospheres and allowing the acquisition of a neuron-like morphology, as well as of immature rat cortical neurons. This protein used here as coating agent may be suggested for the development of scaffolds for tissue regeneration or anti-tumour devices. Copyright © 2016 John Wiley & Sons, Ltd.

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Cryo-Electron Microscopy Structure of Human Peroxiredoxin-3 Filament Reveals the Assembly of a Putative Chaperone

Cited by 31 publications

References 36 publications

Disassembly of the ring‐type decameric structure of peroxiredoxin from Aeropyrum pernix K1 by amino acid mutation

Disassembly of the ring‐type decameric structure of peroxiredoxin from Aeropyrum pernix K1 by amino acid mutation

Formation of supramolecular protein structures on gold surfaces

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

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