scholarly journals Reducing the Amyloidogenicity of Functional Amyloid Protein FapC Increases Its Ability To Inhibit α-Synuclein Fibrillation

ACS Omega ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. 4029-4039 ◽  
Author(s):  
Line Friis Bakmann Christensen ◽  
Kirstine Friis Jensen ◽  
Janni Nielsen ◽  
Brian Stougaard Vad ◽  
Gunna Christiansen ◽  
...  
Keyword(s):  
Amyloid Protein ◽  
Functional Amyloid

Bacterial Model Membranes Reshape Fibrillation of a Functional Amyloid Protein

Biochemistry ◽  
2018 ◽  
Vol 57 (35) ◽  
pp. 5230-5238 ◽  
Author(s):  
Ravit Malishev ◽  
Razan Abbasi ◽  
Raz Jelinek ◽  
Liraz Chai
Keyword(s):  
Model Membranes ◽  
Amyloid Protein ◽  
Functional Amyloid ◽  
Bacterial Model

Colloidal-like aggregation of a functional amyloid protein

2020 ◽  
Vol 22 (40) ◽  
pp. 23286-23294
Author(s):  
David N. Azulay ◽  
Mnar Ghrayeb ◽  
Ilanit Bensimhon Ktorza ◽  
Ido Nir ◽  
Rinad Nasser ◽  
...  
Keyword(s):  
Protein Aggregates ◽  
Amyloid Protein ◽  
Functional Amyloid ◽  
Acidic Conditions

TasA, a bacterial functional amyloid protein, aggregates in a colloidal – like mechanism upon exposure to acidic conditions.

Structure of a Functional Amyloid Protein Subunit Computed Using Sequence Variation

2014 ◽  
Vol 137 (1) ◽  
pp. 22-25 ◽  
Author(s):  
Pengfei Tian ◽  
Wouter Boomsma ◽  
Yong Wang ◽  
Daniel E. Otzen ◽  
Mogens H. Jensen ◽  
...  
Keyword(s):  
Sequence Variation ◽  
Amyloid Protein ◽  
Protein Subunit ◽  
Functional Amyloid

scholarly journals Imperfect repeats in the functional amyloid protein FapC reduce the tendency to fragment during fibrillation

2019 ◽  
Vol 28 (3) ◽  
pp. 633-642 ◽  
Author(s):  
Casper B. Rasmussen ◽  
Gunna Christiansen ◽  
Brian S. Vad ◽  
Carina Lynggaard ◽  
Jan J. Enghild ◽  
...  
Keyword(s):  
Amyloid Protein ◽  
Functional Amyloid

scholarly journals Quantitating denaturation by formic acid: Imperfect repeats are essential to the stability of the functional amyloid protein FapC

2020 ◽  
Author(s):  
Line Friis Bakmann Christensen ◽  
Jan Stanislaw Nowak ◽  
Thorbjørn Vincent Sønderby ◽  
Signe Andrea Frank ◽  
Daniel Erik Otzen
Keyword(s):  
Formic Acid ◽  
Mechanical Stability ◽  
Complete Removal ◽  
Amyloid Formation ◽  
Amyloid Protein ◽  
Biological Functions ◽  
Functional Amyloid ◽  
High Concentrations ◽  
Functional Amyloids ◽  
The Stability

ABSTRACTBacterial functional amyloids are evolutionarily optimized to aggregate to help them fulfil their biological functions, e.g. to provide mechanical stability to biofilm. Amyloid is formed in Pseudomonas sp. by the protein FapC which contains 3 imperfect repeats connected by long linkers. Stepwise removal of these repeats slows down aggregation and increases the propensity of amyloids to fragment during the fibrillation process, but how these mechanistic properties link to fibril stability is unclear. Here we address this question. The extreme robustness of functional amyloid makes them resistant to conventional chemical denaturants, but they dissolve in formic acid (FA) at high concentrations. To quantify this, we first measured the denaturing potency of FA using 3 small acid-resistant proteins (S6, lysozyme and ubiquitin). This revealed a linear relationship between [FA] and the free energy of unfolding with a slope of mFA, as well as a robust correlation between protein residue size and mFA. We then measured the solubilisation of fibrils formed from different FapC variants (with varying number of repeats) as a function of [FA]. The resulting mFA values revealed a decline in the number of residues driving amyloid formation when at least 2 repeats were deleted. The midpoint of denaturation declined monotonically with progressive removal of repeats and correlated with solubility in SDS. Complete removal of all repeats led to fibrils which were solubilized at FA concentrations 2-3 orders of magnitude lower than the repeat-containing variants, showing that at least one imperfect repeat is required for the stability of functional amyloid.

scholarly journals Dual functionality of the TasA amyloid protein inBacillusphysiology and fitness on the phylloplane

2019 ◽  
Author(s):  
Jesús Cámara-Almirón ◽  
Yurena Navarro ◽  
M. Concepción Magno-Pérez-Bryan ◽  
Carlos Molina-Santiago ◽  
John R. Pearson ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Membrane Dynamics ◽  
Fiber Formation ◽  
Membrane Microdomains ◽  
Amyloid Protein ◽  
Functional Amyloid ◽  
Functional Membrane ◽  
Bacterial Fitness ◽  
Amyloid Fiber Formation ◽  
The Individual

AbstractBacteria can form biofilms that consist of multicellular communities embedded in an extracellular matrix (ECM). Previous studies have demonstrated that genetic pathways involved in biofilm formation are activated under a variety of environmental conditions to enhance bacterial fitness; however, the functions of the individual ECM components are still poorly understood. InBacillus subtilis, the main protein component of the ECM is the functional amyloid TasA. In this study, we demonstrate that beyond their well-known defect in biofilm formation,ΔtasAcells also exhibit a range of cytological symptoms indicative of excessive cellular stress, including DNA damage accumulation, changes in membrane potential, higher susceptibility to oxidative stress, and alterations in membrane dynamics. Collectively, these events can lead to increased programmed cell death in the colony. We show that these major physiological changes inΔtasAcells are likely independent of the structural role of TasA during amyloid fiber formation in the ECM. The presence of TasA in cellular membranes, which would place it in proximity to functional membrane microdomains, and mislocalization of the flotillin-like protein FloT inΔtasAcells, led us to propose a role for TasA in the stabilization of membrane dynamics as cells enter stationary phase. We found that these alterations caused by the absence of TasA impair the survival, colonization and competition ofBacilluscells on the phylloplane. Taken together, our results allow the separation of two complementary roles of this functional amyloid protein: i) structural functions during ECM assembly and interactions with plants, and ii) a physiological function in which TasA, via its localization to the cell membrane, stabilizes membrane dynamics and supports more effective cellular adaptation to environmental cues.

scholarly journals What does Evolution Tell us about the Structure of a Functional Amyloid Protein?

2015 ◽  
Vol 108 (2) ◽  
pp. 227a
Author(s):  
Pengfei Tian ◽  
Wouter Boomsma ◽  
Yong Wang ◽  
Daniel Erik Otzen ◽  
Mogens Høgh Jensen ◽  
...  
Keyword(s):  
Amyloid Protein ◽  
Functional Amyloid

scholarly journals Quantitating denaturation by formic acid: imperfect repeats are essential to the stability of the functional amyloid protein FapC

2020 ◽  
Vol 295 (37) ◽  
pp. 13031-13046
Author(s):  
Line Friis Bakmann Christensen ◽  
Jan Stanislaw Nowak ◽  
Thorbjørn Vincent Sønderby ◽  
Signe Andrea Frank ◽  
Daniel Erik Otzen
Keyword(s):  
Formic Acid ◽  
Complete Removal ◽  
Systematic Investigation ◽  
Amyloid Formation ◽  
Amyloid Protein ◽  
Functional Amyloid ◽  
Protein Size ◽  
High Concentrations ◽  
Functional Amyloids ◽  
The Stability

Bacterial functional amyloids are evolutionarily optimized to aggregate, so much so that the extreme robustness of functional amyloid makes it very difficult to examine their structure-function relationships in a detailed manner. Previous work has shown that functional amyloids are resistant to conventional chemical denaturants, but they dissolve in formic acid (FA) at high concentrations. However, systematic investigation requires a quantitative analysis of FA's ability to denature proteins. Amyloid formed by Pseudomonas sp. protein FapC provides an excellent model to investigate FA denaturation. It contains three imperfect repeats, and stepwise removal of these repeats slows fibrillation and increases fragmentation during aggregation. However, the link to stability is unclear. We first calibrated FA denaturation using three small, globular, and acid-resistant proteins. This revealed a linear relationship between the concentration of FA and the free energy of unfolding with a slope of mFA+pH (the combined contribution of FA and FA-induced lowering of pH), as well as a robust correlation between protein size and mFA+pH. We then measured the solubilization of fibrils formed from different FapC variants with varying numbers of repeats as a function of the concentration of FA. This revealed a decline in the number of residues driving amyloid formation upon deleting at least two repeats. The midpoint of denaturation declined with the removal of repeats. Complete removal of all repeats led to fibrils that were solubilized at FA concentrations 2–3 orders of magnitude lower than the repeat-containing variants, showing that at least one repeat is required for the stability of functional amyloid.

Immunocytochemical Localization of Amyloid Protein AA in the “Dense Fibrillar Inclusions” of the Reticuloendothelical Cells

1977 ◽  
Vol 35 ◽  
pp. 438-439
Author(s):  
T. Shirahama ◽  
M. Skinner ◽  
A.S. Cohen
Keyword(s):  
Amyloid Fibril ◽  
Close Association ◽  
Gel Filtration ◽  
Fibril Formation ◽  
Amyloid Protein ◽  
Electron Microscopic ◽  
Amyloid Deposits ◽  
Amyloid Fibril Formation ◽  
Electron Microscopic Technique ◽  
Lysosomal System

A1thought the mechanisms of amyloidogenesis have not been entirely clarified, proteolysis of the parent proteins may be one of the important steps in the amyloid fibril formation. Recently, we reported that "dense fibrillar inclusions" (DFI), which had the characteristics of lysosomes and contained organized fibrillar profiles as well, were observed in the reticuloendothelial cells in close association with the foci of new amyloid deposits. We considered the findings as evidence for the involvement of lysosomal system in amyloid fibril formation (l). In the present study, we attempted to determine the identity of the contents of the DFI by the use of antisera against the amyloid protein (AA) and an immuno-electron microscopic technique.Amyloidosis was induced in CBA/J mice by daily injections of casein (l). AA was isolated from amyloid-laden spleens by gel filtration and antibody to it was produced in rabbits (2). For immunocytochemistry, the unlabeled antibody enzyme method (3) was employed.

Functional amyloid: widespread in Nature, diverse in purpose

2014 ◽  
Vol 56 ◽  
pp. 207-219 ◽  
Author(s):  
Chi L.L. Pham ◽  
Ann H. Kwan ◽  
Margaret Sunde
Keyword(s):  
Spider Silk ◽  
Epigenetic Inheritance ◽  
Fibrillar Structure ◽  
Cytoplasmic Polyadenylation ◽  
Functional Amyloid ◽  
Interacting Protein ◽  
Diverse Range ◽  
Element Binding Protein ◽  
Functional Amyloids ◽  
Micro Organisms

Amyloids are insoluble fibrillar protein deposits with an underlying cross-β structure initially discovered in the context of human diseases. However, it is now clear that the same fibrillar structure is used by many organisms, from bacteria to humans, in order to achieve a diverse range of biological functions. These functions include structure and protection (e.g. curli and chorion proteins, and insect and spider silk proteins), aiding interface transitions and cell–cell recognition (e.g. chaplins, rodlins and hydrophobins), protein control and storage (e.g. Microcin E492, modulins and PMEL), and epigenetic inheritance and memory [e.g. Sup35, Ure2p, HET-s and CPEB (cytoplasmic polyadenylation element-binding protein)]. As more examples of functional amyloid come to light, the list of roles associated with functional amyloids has continued to expand. More recently, amyloids have also been implicated in signal transduction [e.g. RIP1/RIP3 (receptor-interacting protein)] and perhaps in host defence [e.g. aDrs (anionic dermaseptin) peptide]. The present chapter discusses in detail functional amyloids that are used in Nature by micro-organisms, non-mammalian animals and mammals, including the biological roles that they play, their molecular composition and how they assemble, as well as the coping strategies that organisms have evolved to avoid the potential toxicity of functional amyloid.

Sign in / Sign up

Export Citation Format

Share Document