Role of monomer arrangement in the amyloid self-assembly

Portillo, Alexander M.; Hashemi, Mohtadin; Zhang, Yuliang; Breydo, Leonid; Uversky, Vladimir N.; Lyubchenko, Yuri L.

doi:10.1016/j.bbapap.2014.12.009

Cited by 22 publications

(23 citation statements)

References 42 publications

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“…1b ) like those observed for full size Aβ proteins, the presence of non-native species can produce vastly different morphologies. The hairpin peptide forms globular features, like those for GNNQQNY peptide 30 , with no evidence of the formation of fibrils or protofibrils (Fig. 1c ).…”

Section: Resultsmentioning

confidence: 95%

“…30. Briefly, AFM probes (MSNL, Bruker, CA) were cleaned with ethanol and water, followed by treatment with UV (λ 366 nm) light for 45 min.…”

Section: Methodsmentioning

confidence: 99%

“…The peptide immobilization procedures on the AFM tip and mica surfaces were performed as described in ref. 30 . Briefly, AFM probes (MSNL, Bruker, CA) were cleaned with ethanol and water, followed by treatment with UV (λ 366 nm) light for 45 min.…”

Section: Methodsmentioning

confidence: 99%

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Nano-assembly of amyloid β peptide: role of the hairpin fold

Maity

Hashemi

Lyubchenko

2017

Sci Rep

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Structural investigations have revealed that β hairpin structures are common features in amyloid fibrils, suggesting that these motifs play an important role in amyloid assembly. To test this hypothesis, we characterized the effect of the hairpin fold on the aggregation process using a model β hairpin structure, consisting of two Aβ(14–23) monomers connected by a turn forming YNGK peptide. AFM studies of the assembled aggregates revealed that the hairpin forms spherical structures whereas linear Aβ(14–23) monomers form fibrils. Additionally, an equimolar mixture of the monomer and the hairpin assembles into non-fibrillar aggregates, demonstrating that the hairpin fold dramatically changes the morphology of assembled amyloid aggregates. To understand the molecular mechanism underlying the role of the hairpin fold on amyloid assembly, we performed single-molecule probing experiments to measure interactions between hairpin and monomer and two hairpin complexes. The studies reveal that the stability of hairpin-monomer complexes is much higher than hairpin-hairpin complexes. Molecular dynamics simulations revealed a novel intercalated complex for the hairpin and monomer and Monte Carlo modeling further demonstrated that such nano-assemblies have elevated stability compared with stability of the dimer formed by Aβ(14–23) hairpin. The role of such folding on the amyloid assembly is also discussed.

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Section: Resultsmentioning

confidence: 95%

“…30. Briefly, AFM probes (MSNL, Bruker, CA) were cleaned with ethanol and water, followed by treatment with UV (λ 366 nm) light for 45 min.…”

Section: Methodsmentioning

confidence: 99%

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Nano-assembly of amyloid β peptide: role of the hairpin fold

Maity

Hashemi

Lyubchenko

2017

Sci Rep

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“…The force curve was approximated with the worm like chain (WLC) model, 34 and the rupture force value was calculated from this approximation. 18, 35 Experiments were performed at pH 7 and pH 3.7, and several hundred force curves were assembled into histograms for each pH value.…”

Section: Resultsmentioning

confidence: 99%

Single-molecule probing of amyloid nano-ensembles using the polymer nanoarray approach

Maity

Viazovkina

Gall

et al. 2017

Phys. Chem. Chem. Phys.

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Soluble amyloid-beta (Aβ) oligomers are the prime causitive agents of cognitive deficits during early stages of Alzheimer’s disease (AD). The transient nature of the oligomers makes them difficult to characterize by traditional techniques, suggesting that advanced approaches are necessary. Previously developed fluorescence-based tethered approach for probing intermolecular interactions (TAPIN) and AFM-based single-molecule force spectroscopy are capable of probing dimers of Aβ peptides. In this paper, a novel polymer nanoarray approach to probe trimers and tetramers formed by the Aβ(14–23) segment of Aβ protein at the single-molecule level is applied. By using this approach combined with TAPIN and AFM force spectroscopy, the impact of pH on the assembly of these oligomers was characterized. Experimental results reveal that pH affects the oligomer assembly process. At neutral pH, trimers and tetramers assemble into structures with a similar stability, while at acidic conditions (pH 3.7), the oligomers adopt a set of structures with different lifetimes and strengths. Models for the assembly of Aβ(14–23) trimers and tetramers based on the results obtained is proposed.

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“…1,2 Growth of amyloids occurs by the nucleated polymerization of soluble proteins of a particular sequence. 3,4 Many proteins can polymerize to form amyloid when provided an appropriate environment in vitro, indicating this as inherent characteristic of polypeptides. Indeed, many recent studies have shown the existence of beneficial amyloids that are important for survival of a host organism.…”

Section: Introductionmentioning

confidence: 99%

The small heat shock protein Hsp31 cooperates with Hsp104 to modulate Sup35 prion aggregation

Aslam

Tsai

Hazbun

2016

Prion

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The yeast homolog of DJ-1, Hsp31, is a multifunctional protein that is involved in several cellular pathways including detoxification of the toxic metabolite methylglyoxal and as a protein deglycase. Prior studies ascribed Hsp31 as a molecular chaperone that can inhibit α-Syn aggregation in vitro and alleviate its toxicity in vivo. It was also shown that Hsp31 inhibits Sup35 aggregate formation in yeast, however, it is unknown if Hsp31 can modulate [PSI] phenotype and Sup35 prionogenesis. Other small heat shock proteins, Hsp26 and Hsp42 are known to be a part of a synergistic proteostasis network that inhibits Sup35 prion formation and promotes its disaggregation. Here, we establish that Hsp31 inhibits Sup35 [PSI] prion formation in collaboration with a well-known disaggregase, Hsp104. Hsp31 transiently prevents prion induction but does not suppress induction upon prolonged expression of Sup35 indicating that Hsp31 can be overcome by larger aggregates. In addition, elevated levels of Hsp31 do not cure [PSI] strains indicating that Hsp31 cannot intervene in a pre-existing prion oligomerization cycle. However, Hsp31 can modulate prion status in cooperation with Hsp104 because it inhibits Sup35 aggregate formation and potentiates [PSI] prion curing upon overexpression of Hsp104. The absence of Hsp31 reduces [PSI] prion curing by Hsp104 without influencing its ability to rescue cellular thermotolerance. Hsp31 did not synergize with Hsp42 to modulate the [PSI] phenotype suggesting that both proteins act on similar stages of the prion cycle. We also showed that Hsp31 physically interacts with Hsp104 and together they prevent Sup35 prion toxicity to greater extent than if they were expressed individually. These results elucidate a mechanism for Hsp31 on prion modulation that suggest it acts at a distinct step early in the Sup35 aggregation process that is different from Hsp104. This is the first demonstration of the modulation of [PSI] status by the chaperone action of Hsp31. The delineation of Hsp31's role in the chaperone cycle has implications for understanding the role of the DJ-1 superfamily in controlling misfolded proteins in neurodegenerative disease and cancer.

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Role of monomer arrangement in the amyloid self-assembly

Cited by 22 publications

References 42 publications

Nano-assembly of amyloid β peptide: role of the hairpin fold

Nano-assembly of amyloid β peptide: role of the hairpin fold

Single-molecule probing of amyloid nano-ensembles using the polymer nanoarray approach

The small heat shock protein Hsp31 cooperates with Hsp104 to modulate Sup35 prion aggregation

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