Special Issue "Functional Amyloids"

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (15 May 2017)

Special Issue Editors

Guest Editor
A/Prof. Dr. Margaret Sunde

School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia
Website | E-Mail
Interests: amyloid fibril formation and structure; functional amyloids; hydrophobins; protein misfolding; necroptosis
Guest Editor
A/Prof. Dr. Matthew Chapman

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
Website | E-Mail
Interests: microbiology; functional amyloid; protein secretion; extracellular matrix
Guest Editor
Prof. Dr. Daniel Otzen

Interdisciplinary Nanoscience Centre and Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark
Website | E-Mail
Interests: functional bacterial amyloid; pathological amyloid; mechanisms of fibrillation in vivo and in vitro; structure of oligomers and fibrils
Guest Editor
Prof. Dr. Sarah Perrett

Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China
Website | E-Mail
Interests: protein folding; post-translational modification and quality control; functional amyloids; amyloid-based nanomaterials

Special Issue Information

Dear Colleagues,

There is a growing recognition that the cross β amyloid architecture is found widely in nature, formed by the self-assembly of different proteins and associated with multiple and diverse aspects of normal biology in organisms from microbes to mammals. In so-called “functional amyloid” the amyloidogenic proteins provide desirable self-assembly capability and the biologically active form of the protein is retained or generated in the fibrillar form. The amyloid, multimeric version of the protein has properties beyond that of the monomeric component protein. Functional amyloid fibrils have been shown to have roles in bacterial biofilm formation, fungal adhesion and colonisation, melanin sequestration and subcellular localisation of proteins associated with gene regulation. Studies of disease-associated amyloid formation and structure have laid the foundations for investigation of functional amyloids but recent work on the latter is bringing to light some of the differences in the properties of biologically active and pathological amyloids. We hope that this special issue will highlight exciting recent work in this area as well as stimulate new avenues of research into the biological functions of amyloid, the regulation of functional amyloid and the potential application of amyloids as nanomaterials.

Followed by brief mention of different contributions, putting them in context with each other and the overall theme.

A/Prof. Dr. Margaret Sunde
A/Prof. Dr. Matthew Chapman
Prof. Dr. Daniel Otzen
Prof. Dr. Sarah Perrett
Guest Editors

Manuscript Submission Information

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Keywords

  • functional amyloid
  • fibrils
  • aggregation
  • assembly
  • intermediates
  • mechanisms of fibrillation
  • seeding
  • elongation
  • biofilm
  • chaperones

Published Papers (12 papers)

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Research

Jump to: Review

Open AccessArticle Structure-Dependent Interfacial Properties of Chaplin F from Streptomyces coelicolor
Biomolecules 2017, 7(3), 68; doi:10.3390/biom7030068
Received: 27 July 2017 / Revised: 8 September 2017 / Accepted: 12 September 2017 / Published: 19 September 2017
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Abstract
Chaplin F (Chp F) is a secreted surface-active peptide involved in the aerial growth of Streptomyces. While Chp E demonstrates a pH-responsive surface activity, the relationship between Chp F structure, function and the effect of solution pH is unknown. Chp F peptides
[...] Read more.
Chaplin F (Chp F) is a secreted surface-active peptide involved in the aerial growth of Streptomyces. While Chp E demonstrates a pH-responsive surface activity, the relationship between Chp F structure, function and the effect of solution pH is unknown. Chp F peptides were found to self-assemble into amyloid fibrils at acidic pH (3.0 or the isoelectric point (pI) of 4.2), with ~99% of peptides converted into insoluble fibrils. In contrast, Chp F formed short assemblies containing a mixture of random coil and β-sheet structure at a basic pH of 10.0, where only 40% of the peptides converted to fibrils. The cysteine residues in Chp F did not appear to play a role in fibril assembly. The interfacial properties of Chp F at the air/water interface were altered by the structures adopted at different pH, with Chp F molecules forming a higher surface-active film at pH 10.0 with a lower area per molecule compared to Chp F fibrils at pH 3.0. These data show that the pH responsiveness of Chp F surface activity is the reverse of that observed for Chp E, which could prove useful in potential applications where surface activity is desired over a wide range of solution pH. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessArticle Functional Amyloid Protection in the Eye Lens: Retention of α-Crystallin Molecular Chaperone Activity after Modification into Amyloid Fibrils
Biomolecules 2017, 7(3), 67; doi:10.3390/biom7030067
Received: 13 July 2017 / Revised: 21 August 2017 / Accepted: 7 September 2017 / Published: 12 September 2017
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Abstract
Amyloid fibril formation occurs from a wide range of peptides and proteins and is typically associated with a loss of protein function and/or a gain of toxic function, as the native structure of the protein undergoes major alteration to form a cross β-sheet
[...] Read more.
Amyloid fibril formation occurs from a wide range of peptides and proteins and is typically associated with a loss of protein function and/or a gain of toxic function, as the native structure of the protein undergoes major alteration to form a cross β-sheet array. It is now well recognised that some amyloid fibrils have a biological function, which has led to increased interest in the potential that these so-called functional amyloids may either retain the function of the native protein, or gain function upon adopting a fibrillar structure. Herein, we investigate the molecular chaperone ability of α-crystallin, the predominant eye lens protein which is composed of two related subunits αA- and αB-crystallin, and its capacity to retain and even enhance its chaperone activity after forming aggregate structures under conditions of thermal and chemical stress. We demonstrate that both eye lens α-crystallin and αB-crystallin (which is also found extensively outside the lens) retain, to a significant degree, their molecular chaperone activity under conditions of structural change, including after formation into amyloid fibrils and amorphous aggregates. The results can be related directly to the effects of aging on the structure and chaperone function of α-crystallin in the eye lens, particularly its ability to prevent crystallin protein aggregation and hence lens opacification associated with cataract formation. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessArticle Direct Identification of Functional Amyloid Proteins by Label-Free Quantitative Mass Spectrometry
Biomolecules 2017, 7(3), 58; doi:10.3390/biom7030058
Received: 13 July 2017 / Revised: 30 July 2017 / Accepted: 31 July 2017 / Published: 4 August 2017
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Abstract
Functional amyloids are important structural and functional components of many biofilms, yet our knowledge of these fascinating polymers is limited to a few examples for which the native amyloids have been isolated in pure form. Isolation of the functional amyloids from other cell
[...] Read more.
Functional amyloids are important structural and functional components of many biofilms, yet our knowledge of these fascinating polymers is limited to a few examples for which the native amyloids have been isolated in pure form. Isolation of the functional amyloids from other cell components represents a major bottleneck in the search for new functional amyloid systems. Here we present a label-free quantitative mass spectrometry method that allows identification of amyloid proteins directly in cell lysates. The method takes advantage of the extreme structural stability and polymeric nature of functional amyloids and the ability of concentrated formic acid to depolymerize the amyloids. An automated data processing pipeline that provides a short list of amyloid protein candidates was developed based on an amyloid-specific sigmoidal abundance signature in samples treated with increasing concentrations of formic acid. The method was evaluated using the Escherichia coli curli and the Pseudomonas Fap system. It confidently identified the major amyloid subunit for both systems, as well as the minor subunit for the curli system. A few non-amyloid proteins also displayed the sigmoidal abundance signature. However, only one of these contained a sec-dependent signal peptide, which characterizes most of all secreted proteins, including all currently known functional bacterial amyloids. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessArticle Metal Binding Properties of the N-Terminus of the Functional Amyloid Orb2
Biomolecules 2017, 7(3), 57; doi:10.3390/biom7030057
Received: 3 June 2017 / Revised: 14 July 2017 / Accepted: 21 July 2017 / Published: 1 August 2017
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Abstract
The cytoplasmic polyadenylation element binding protein (CPEB) homologue Orb2 is a functional amyloid that plays a key regulatory role for long-term memory in Drosophila. Orb2 has a glutamine, histidine-rich (Q/H-rich) domain that resembles the Q/H-rich, metal binding domain of the Hpn-like protein
[...] Read more.
The cytoplasmic polyadenylation element binding protein (CPEB) homologue Orb2 is a functional amyloid that plays a key regulatory role for long-term memory in Drosophila. Orb2 has a glutamine, histidine-rich (Q/H-rich) domain that resembles the Q/H-rich, metal binding domain of the Hpn-like protein (Hpnl) found in Helicobacter pylori. In the present study, we used chromatography and isothermal titration calorimetry (ITC) to show that the Q/H-rich domain of Orb2 binds Ni2+ and other transition metals ions with μM affinity. Using site directed mutagenesis, we show that several histidine residues are important for binding. In particular, the H61Y mutation, which was previously shown to affect the aggregation of Orb2 in cell culture, completely inhibited metal binding of Orb2. Finally, we used thioflavin T fluorescence and electron microscopy images to show that Ni2+ binding induces the aggregating of Orb2 into structures that are distinct from the amyloid fibrils formed in the absence of Ni2+. These data suggest that transition metal binding might be important for the function of Orb2 and potentially long-term memory in Drosophila. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessArticle Sequence Identification, Recombinant Production, and Analysis of the Self-Assembly of Egg Stalk Silk Proteins from Lacewing Chrysoperla carnea
Biomolecules 2017, 7(2), 43; doi:10.3390/biom7020043
Received: 10 April 2017 / Revised: 2 June 2017 / Accepted: 7 June 2017 / Published: 13 June 2017
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Abstract
Egg stalk silks of the common green lacewing Chrysoperla carnea likely comprise at least three different silk proteins. Based on the natural spinning process, it was hypothesized that these proteins self-assemble without shear stress, as adult lacewings do not use a spinneret. To
[...] Read more.
Egg stalk silks of the common green lacewing Chrysoperla carnea likely comprise at least three different silk proteins. Based on the natural spinning process, it was hypothesized that these proteins self-assemble without shear stress, as adult lacewings do not use a spinneret. To examine this, the first sequence identification and determination of the gene expression profile of several silk proteins and various transcript variants thereof was conducted, and then the three major proteins were recombinantly produced in Escherichia coli encoded by their native complementary DNA (cDNA) sequences. Circular dichroism measurements indicated that the silk proteins in aqueous solutions had a mainly intrinsically disordered structure. The largest silk protein, which we named ChryC1, exhibited a lower critical solution temperature (LCST) behavior and self-assembled into fibers or film morphologies, depending on the conditions used. The second silk protein, ChryC2, self-assembled into nanofibrils and subsequently formed hydrogels. Circular dichroism and Fourier transform infrared spectroscopy confirmed conformational changes of both proteins into beta sheet rich structures upon assembly. ChryC3 did not self-assemble into any morphology under the tested conditions. Thereby, through this work, it could be shown that recombinant lacewing silk proteins can be produced and further used for studying the fiber formation of lacewing egg stalks. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessArticle Amyloid Fibrils from Hemoglobin
Biomolecules 2017, 7(2), 37; doi:10.3390/biom7020037
Received: 11 January 2017 / Revised: 16 March 2017 / Accepted: 5 April 2017 / Published: 11 April 2017
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Abstract
Amyloid fibrils are a class of insoluble protein nanofibers that are formed via the self-assembly of a wide range of peptides and proteins. They are increasingly exploited for a broad range of applications in bionanotechnology, such as biosensing and drug delivery, as nanowires,
[...] Read more.
Amyloid fibrils are a class of insoluble protein nanofibers that are formed via the self-assembly of a wide range of peptides and proteins. They are increasingly exploited for a broad range of applications in bionanotechnology, such as biosensing and drug delivery, as nanowires, hydrogels, and thin films. Amyloid fibrils have been prepared from many proteins, but there has been no definitive characterization of amyloid fibrils from hemoglobin to date. Here, nanofiber formation was carried out under denaturing conditions using solutions of apo-hemoglobin extracted from bovine waste blood. A characteristic amyloid fibril morphology was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM), with mean fibril dimensions of approximately 5 nm diameter and up to several microns in length. The thioflavin T assay confirmed the presence of β-sheet structures in apo-hemoglobin fibrils, and X-ray fiber diffraction showed the characteristic amyloid cross-β quaternary structure. Apo-hemoglobin nanofibers demonstrated high stability over a range of temperatures (−20 to 80 °C) and pHs (2–10), and were stable in the presence of organic solvents and trypsin, confirming their potential as nanomaterials with versatile applications. This study conclusively demonstrates the formation of amyloid fibrils from hemoglobin for the first time, and also introduces a cost-effective method for amyloid fibril manufacture using meat industry by-products. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Review

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Open AccessReview Why are Functional Amyloids Non-Toxic in Humans?
Biomolecules 2017, 7(4), 71; doi:10.3390/biom7040071
Received: 21 July 2017 / Revised: 18 September 2017 / Accepted: 20 September 2017 / Published: 22 September 2017
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Abstract
Amyloids were first identified in association with amyloidoses, human diseases in which proteins and peptides misfold into amyloid fibrils. Subsequent studies have identified an array of functional amyloid fibrils that perform physiological roles in humans. Given the potential for the production of toxic
[...] Read more.
Amyloids were first identified in association with amyloidoses, human diseases in which proteins and peptides misfold into amyloid fibrils. Subsequent studies have identified an array of functional amyloid fibrils that perform physiological roles in humans. Given the potential for the production of toxic species in amyloid assembly reactions, it is remarkable that cells can produce these functional amyloids without suffering any obvious ill effect. Although the precise mechanisms are unclear, there are a number of ways in which amyloid toxicity may be prevented. These include regulating the level of the amyloidogenic peptides and proteins, minimising the production of prefibrillar oligomers in amyloid assembly reactions, sequestrating amyloids within membrane bound organelles, controlling amyloid assembly by other molecules, and disassembling the fibrils under physiological conditions. Crucially, a better understanding of how toxicity is avoided in the production of functional amyloids may provide insights into the prevention of amyloid toxicity in amyloidoses. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessReview The Physiological and Pathological Implications of the Formation of Hydrogels, with a Specific Focus on Amyloid Polypeptides
Biomolecules 2017, 7(4), 70; doi:10.3390/biom7040070
Received: 20 July 2017 / Revised: 30 August 2017 / Accepted: 18 September 2017 / Published: 22 September 2017
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Abstract
Hydrogels are water-swollen and viscoelastic three-dimensional cross-linked polymeric network originating from monomer polymerisation. Hydrogel-forming polypeptides are widely found in nature and, at a cellular and organismal level, they provide a wide range of functions for the organism making them. Amyloid structures, arising from
[...] Read more.
Hydrogels are water-swollen and viscoelastic three-dimensional cross-linked polymeric network originating from monomer polymerisation. Hydrogel-forming polypeptides are widely found in nature and, at a cellular and organismal level, they provide a wide range of functions for the organism making them. Amyloid structures, arising from polypeptide aggregation, can be damaging or beneficial to different types of organisms. Although the best-known amyloids are those associated with human pathologies, this underlying structure is commonly used by higher eukaryotes to maintain normal cellular activities, and also by microbial communities to promote their survival and growth. Amyloidogenesis occurs by nucleation-dependent polymerisation, which includes several species (monomers, nuclei, oligomers, and fibrils). Oligomers of pathological amyloids are considered the toxic species through cellular membrane perturbation, with the fibrils thought to represent a protective sink for toxic species. However, both functional and disease-associated amyloids use fibril cross-linking to form hydrogels. The properties of amyloid hydrogels can be exploited by organisms to fulfil specific physiological functions. Non-physiological hydrogelation by pathological amyloids may provide additional toxic mechanism(s), outside of membrane toxicity by oligomers, such as physical changes to the intracellular and extracellular environments, with wide-spread consequences for many structural and dynamic processes, and overall effects on cell survival. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessReview The Role of Functional Amyloids in Multicellular Growth and Development of Gram-Positive Bacteria
Biomolecules 2017, 7(3), 60; doi:10.3390/biom7030060
Received: 7 July 2017 / Revised: 1 August 2017 / Accepted: 3 August 2017 / Published: 7 August 2017
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Abstract
Amyloid fibrils play pivotal roles in all domains of life. In bacteria, these fibrillar structures are often part of an extracellular matrix that surrounds the producing organism and thereby provides protection to harsh environmental conditions. Here, we discuss the role of amyloid fibrils
[...] Read more.
Amyloid fibrils play pivotal roles in all domains of life. In bacteria, these fibrillar structures are often part of an extracellular matrix that surrounds the producing organism and thereby provides protection to harsh environmental conditions. Here, we discuss the role of amyloid fibrils in the two distant Gram-positive bacteria, Streptomyces coelicolor and Bacillus subtilis. We describe how amyloid fibrils contribute to a multitude of developmental processes in each of these systems, including multicellular growth and community development. Despite this variety of tasks, we know surprisingly little about how their assembly is organized to fulfill all these roles. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessReview Functional Amyloids in Reproduction
Biomolecules 2017, 7(3), 46; doi:10.3390/biom7030046
Received: 6 June 2017 / Revised: 20 June 2017 / Accepted: 23 June 2017 / Published: 29 June 2017
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Abstract
Amyloids are traditionally considered pathological protein aggregates that play causative roles in neurodegenerative disease, diabetes and prionopathies. However, increasing evidence indicates that in many biological systems nonpathological amyloids are formed for functional purposes. In this review, we will specifically describe amyloids that carry
[...] Read more.
Amyloids are traditionally considered pathological protein aggregates that play causative roles in neurodegenerative disease, diabetes and prionopathies. However, increasing evidence indicates that in many biological systems nonpathological amyloids are formed for functional purposes. In this review, we will specifically describe amyloids that carry out biological roles in sexual reproduction including the processes of gametogenesis, germline specification, sperm maturation and fertilization. Several of these functional amyloids are evolutionarily conserved across several taxa, including human, emphasizing the critical role amyloids perform in reproduction. Evidence will also be presented suggesting that, if altered, some functional amyloids may become pathological. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessReview Applications of Functional Amyloids from Fungi: Surface Modification by Class I Hydrophobins
Biomolecules 2017, 7(3), 45; doi:10.3390/biom7030045
Received: 15 May 2017 / Revised: 20 June 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
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Abstract
Class I hydrophobins produced from fungi are amongst the first proteins recognized as functional amyloids. They are amphiphilic proteins involved in the formation of aerial structures such as spores or fruiting bodies. They form chemically robust layers which can only be dissolved in
[...] Read more.
Class I hydrophobins produced from fungi are amongst the first proteins recognized as functional amyloids. They are amphiphilic proteins involved in the formation of aerial structures such as spores or fruiting bodies. They form chemically robust layers which can only be dissolved in strong acids. These layers adhere to different surfaces, changing their wettability, and allow the binding of other proteins. Herein, the modification of diverse types of surfaces with Class I hydrophobins is reported, highlighting the applications of the coated surfaces. Indeed, these coatings can be exploited in several fields, spanning from biomedical to industrial applications, which include biosensing and textile manufacturing. Full article
(This article belongs to the Special Issue Functional Amyloids)
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Open AccessReview Diversity of Amyloid Motifs in NLR Signaling in Fungi
Biomolecules 2017, 7(2), 38; doi:10.3390/biom7020038
Received: 2 March 2017 / Revised: 10 April 2017 / Accepted: 10 April 2017 / Published: 13 April 2017
Cited by 2 | PDF Full-text (2756 KB) | HTML Full-text | XML Full-text
Abstract
Amyloid folds not only represent the underlying cause of a large class of human diseases but also display a variety of functional roles both in prokaryote and eukaryote organisms. Among these roles is a recently-described activity in signal transduction cascades functioning in host
[...] Read more.
Amyloid folds not only represent the underlying cause of a large class of human diseases but also display a variety of functional roles both in prokaryote and eukaryote organisms. Among these roles is a recently-described activity in signal transduction cascades functioning in host defense and programmed cell death and involving Nod-like receptors (NLRs). In different fungal species, prion amyloid folds convey activation signals from a receptor protein to an effector domain by an amyloid templating and propagation mechanism. The discovery of these amyloid signaling motifs derives from the study of [Het-s], a fungal prion of the species Podospora anserina. These signaling pathways are typically composed of two basic components encoded by adjacent genes, the NLR receptor bearing an amyloid motif at the N-terminal end and a cell death execution protein with a HeLo pore-forming domain bearing a C-terminal amyloid motif. Activation of the NLR receptor allows for amyloid folding of the N-terminal amyloid motifs which then template trans-conformation of the homologous motif in the cell death execution protein. A variety of such motifs, which differ by their sequence signature, have been described in fungi. Among them, the PP-motif bears resemblance with the RHIM amyloid motif involved in the necroptosis pathway in mammals suggesting an evolutionary conservation of amyloid signaling from fungi to mammals. Full article
(This article belongs to the Special Issue Functional Amyloids)
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