The cytotoxic
            <i>Staphylococcus aureus</i>
            PSMα3 reveals a cross-α amyloid-like fibril

Tayeb-Fligelman, Einav; Tabachnikov, Orly; Moshe, Asher; Goldshmidt-Tran, Orit; Sawaya, M.R.; Coquelle, Nicolas; Colletier, J.P.; Landau, Meytal

doi:10.1126/science.aaf4901

Cited by 258 publications

(394 citation statements)

References 71 publications

(43 reference statements)

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“…However, a recent study reported a cross-α amyloid structure associated with PSMα3, a 22-residue functional amyloid peptide secreted by Staphylococcus aureus for inflammatory response stimulation, human cell lysis and biofilm formation, representing a surprising departure from the common amyloid structure. 517 The suprastructure of amyloid fibrils – including that of all (S) Aβ 1–40 and hen egg lysozyme – has been shown as predominantly left handed, 518 originated from the inherent left-handed chirality of the (S) amino acids. However, right-handed amyloids have been reported for truncated serum amyloid A (SAA) peptides (< 12 residues), resulting from the occurrence of β helices in SAA protofilaments prior to their assembly into fibrils.…”

Section: Discussionmentioning

confidence: 99%

Implications of peptide assemblies in amyloid diseases

et al. 2017

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Neurodegenerative disorders and type 2 diabetes are global epidemics compromising the quality of life of millions worldwide, with profound social and economic implications. Despite the significant differences in pathology – much of which are poorly understood – these diseases are commonly characterized by the presence of cross-β amyloid fibrils as well as the loss of neuronal or pancreatic β-cells. In this review, we document research progress on the molecular and mesoscopic self-assembly of amyloid-beta, alpha synuclein, human islet amyloid polypeptide and prions, the peptides and proteins associated with Alzheimer’s, Parkinson’s, type 2 diabetes and prions diseases. In addition, we discuss the toxicities of these amyloid proteins based on their self-assembly as well as their interactions with membranes, metal ions, small molecules and engineered nanoparticles. Through this presentation we show the remarkable similarities and differences in the structural transitions of the amyloid proteins through primary and secondary nucleation, the common evolution from disordered monomers to alpha-helices and then to β-sheets when the proteins encounter the cell membrane, and, the consensus (with a few exceptions) that off-pathway oligomers, rather than amyloid fibrils, are the toxic species regardless of the pathogenic protein sequence or physicochemical properties. In addition, we highlight the crucial role of molecular self-assembly in eliciting the biological and pathological consequences of the amyloid proteins within the context of their cellular environments and their spreading between cells and organs. Exploiting such structure-function-toxicity relationship may prove pivotal for the detection and mitigation of amyloid diseases.

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Section: Discussionmentioning

confidence: 99%

Implications of peptide assemblies in amyloid diseases

et al. 2017

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“…Recently, bacterial peptides have also been shown to form α-helical structural motifs that assemble into fibers. 23 …”

Section: Introductionmentioning

confidence: 99%

Amyloid β-Sheet Secondary Structure Identified in UV-Induced Cataracts of Porcine Lenses using 2D IR Spectroscopy

Zhang

Alperstein

Zanni

2017

Journal of Molecular Biology

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Cataracts are formed by the aggregation of crystallin proteins in the eye lens. Many in vitro studies have established that crystallin proteins precipitate into aggregates that contain amyloid fibers when denatured, but there is little evidence that ex vivo cataracts contain amyloid. In this study, we collect two dimensional infrared (2D IR) spectra on tissue slices of porcine eye lenses. As shown in control experiments on in vitro αB- and γD-crystallin, 2D IR spectroscopy can identify amyloidogenic β-sheet secondary structure because this structure has exceptionally strong coupling and a high degree of ordering that creates characteristic diagonal and cross peaks. In ex vivo experiments of acid treated tissues, characteristic 2D IR features are observed and fibers >50 nm in length are resolved by TEM, consistent with amyloid fibers. In UV-irradiated lens tissues, fibers are not observed with TEM, but amyloidogenic β-sheet secondary structure is identified from the 2D IR spectra. The characteristic 2D IR features of amyloid β-sheet secondary structure are created by as few as 4 or 5 strands, and so identify amyloid secondary structure even if the aggregates themselves are too small to be resolved with TEM. We discuss these findings in the context of the chaperone system of the lens, which we hypothesize sequesters small aggregates, thereby preventing long fibers from forming. This study expands the scope of heterodyned 2D IR spectroscopy to tissues. The results provide a link between in vitro and ex vivo studies, and support the hypothesis that cataracts is an amyloid disease.

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“…Two helices, formed by 28mers, wrapped around one another to form a dimer, with complete 3.5 residues per turn mediated by multiple hydrogen bonds. [149] Recently, it was reported that certain bacterial amyloids are α-helices,[150] implying that it should be feasible to use α-helices for generating supramolecular hydrogels.…”

Section: Supramolecular Hydrogels Made Of the Basic Biological Buimentioning

confidence: 99%

Supramolecular biofunctional materials

et al. 2017

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This review discusses supramolecular biofunctional materials, a novel class of biomaterials formed by small molecules that are held together via noncovalent interactions. The complexity of biology and relevant biomedical problems not only inspire, but also demand effective molecular design for functional materials. Supramolecular biofunctional materials offer (almost) unlimited possibilities and opportunities to address challenging biomedical problems. Rational molecular design of supramolecular biofunctional materials exploit powerful and versatile noncovalent interactions, which offer many advantages, such as responsiveness, reversibility, tunability, biomimicry, modularity, predictability, and, most importantly, adaptiveness. In this review, besides elaborating on the merits of supramolecular biofunctional materials (mainly in the form of hydrogels and/or nanoscale assemblies) resulting from noncovalent interactions, we also discuss the advantages of small peptides as a prevalent molecular platform to generate a wide range of supramolecular biofunctional materials for the applications in drug delivery, tissue engineering, immunology, cancer therapy, fluorescent imaging, and stem cell regulation. This review aims to provide a brief synopsis of recent achievements at the intersection of supramolecular chemistry and biomedical science in hope of contributing to the multidisciplinary research on supramolecular biofunctional materials for a wide range of applications. We envision that supramolecular biofunctional materials will contribute to the development of new therapies that will ultimately lead to a paradigm shift for developing next generation biomaterials for medicine.

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The cytotoxic Staphylococcus aureus PSMα3 reveals a cross-α amyloid-like fibril

Cited by 258 publications

References 71 publications

Implications of peptide assemblies in amyloid diseases

Implications of peptide assemblies in amyloid diseases

Amyloid β-Sheet Secondary Structure Identified in UV-Induced Cataracts of Porcine Lenses using 2D IR Spectroscopy

Supramolecular biofunctional materials

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