scholarly journals Kinetics of amyloid formation and membrane interaction with amyloidogenic proteins

2007 ◽  
Vol 1768 (8) ◽  
pp. 1923-1934 ◽  
Author(s):  
Regina M. Murphy
Keyword(s):  
Amyloid Formation ◽  
Membrane Interaction ◽  
Amyloidogenic Proteins ◽  
Kinetics Of

scholarly journals Implications of Metal Binding and Asparagine Deamidation for Amyloid Formation

2018 ◽  
Vol 19 (8) ◽  
pp. 2449 ◽  
Author(s):  
Yutaka Sadakane ◽  
Masahiro Kawahara
Keyword(s):  
Conformational Changes ◽  
Posttranslational Modifications ◽  
Self Assembly ◽  
Metal Binding ◽  
Prion Diseases ◽  
Amyloid Formation ◽  
Amyloidogenic Proteins ◽  
Two Factors ◽  
Asparagine Deamidation ◽  
Β Amyloid

Increasing evidence suggests that amyloid formation, i.e., self-assembly of proteins and the resulting conformational changes, is linked with the pathogenesis of various neurodegenerative disorders such as Alzheimer’s disease, prion diseases, and Lewy body diseases. Among the factors that accelerate or inhibit oligomerization, we focus here on two non-genetic and common characteristics of many amyloidogenic proteins: metal binding and asparagine deamidation. Both reflect the aging process and occur in most amyloidogenic proteins. All of the amyloidogenic proteins, such as Alzheimer’s β-amyloid protein, prion protein, and α-synuclein, are metal-binding proteins and are involved in the regulation of metal homeostasis. It is widely accepted that these proteins are susceptible to non-enzymatic posttranslational modifications, and many asparagine residues of these proteins are deamidated. Moreover, these two factors can combine because asparagine residues can bind metals. We review the current understanding of these two common properties and their implications in the pathogenesis of these neurodegenerative diseases.

scholarly journals Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation

2006 ◽  
Vol 87 (8) ◽  
pp. 2443-2449 ◽  
Author(s):  
Patrick A. Lewis ◽  
M. Howard Tattum ◽  
Samantha Jones ◽  
Daljit Bhelt ◽  
Mark Batchelor ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Prion Diseases ◽  
Amyloid Formation ◽  
Native Structure ◽  
Prion Strain ◽  
Profound Influence ◽  
Human Prion Protein ◽  
Kinetics Of ◽  
Codon 129

The human prion protein (PrP) has a common polymorphism at residue 129, which can be valine or methionine. This polymorphism has a strong influence on susceptibility to prion diseases and on prion-strain properties. Previous work has shown that this amino acid variation has no measurable effect on the native structure of cellular PrP (PrPC). Here, it is shown that the polymorphism does not change the efficiency of conversion to the β-PrP conformation or affect the binding of copper(II) ions. However, in a partially denatured conformation, the polymorphic variation has a profound influence on the ability of the protein to form amyloid fibrils spontaneously.

scholarly journals The Kinetics of Amyloid Fibril Formation by de Novo Protein Albebetin and Its Mutant Variants

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 241
Author(s):  
Vitalii Balobanov ◽  
Rita Chertkova ◽  
Anna Egorova ◽  
Dmitry Dolgikh ◽  
Valentina Bychkova ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
De Novo ◽  
Point Mutations ◽  
Inhibitory Effect ◽  
Structural Basis ◽  
Amyloid Formation ◽  
Amyloid Fibril Formation ◽  
External Conditions ◽  
New Perspective ◽  
Kinetics Of

Engineering of amyloid structures is one of the new perspective areas of protein engineering. Studying the process of amyloid formation can help find ways to manage it in the interests of medicine and biotechnology. One of the promising candidates for the structural basis of artificial functional amyloid fibrils is albebetin (ABB), an artificial protein engineered under the leadership of O.B. Ptitsyn. Various aspects of the amyloid formation of this protein and some methods for controlling this process are investigated in this paper. Four stages of amyloid fibrils formation by this protein from the first non-fibrillar aggregates to mature fibrils and large micron-sized complexes have been described in detail. Dependence of albebetin amyloids formation on external conditions and some mutations also have been described. The introduction of similar point mutations in the two structurally identical α-β-β motifs of ABB lead to different amiloidogenesis kinetics. The inhibitory effect of a disulfide bond and high pH on amyloid fibrils formation, that can be used to control this process, was shown. The results of this work are a good basis for the further design and use of ABB-based amyloid constructs.

scholarly journals The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matthias M. Schneider ◽  
Saurabh Gautam ◽  
Therese W. Herling ◽  
Ewa Andrzejewska ◽  
Georg Krainer ◽  
...  
Keyword(s):  
Molecular Chaperones ◽  
De Novo ◽  
Cellular Protein ◽  
Amyloid Formation ◽  
First Order ◽  
Hsp70 Family ◽  
First Order Kinetics ◽  
Reaction Proceeds ◽  
Kinetics Of

AbstractMolecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as α-synuclein fibrils, which accumulate in Parkinson’s disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study α-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse α-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies.

scholarly journals A Biocompatible Fluorescent Probe for the Selective Detection of Amyloid Fibrils

2020 ◽  
Author(s):  
Anirban Das ◽  
Tanoy Dutta ◽  
Laxmikant Gadhe ◽  
Apurba Koner ◽  
Ishu Saraogi
Keyword(s):  
Amyloid Fibrils ◽  
Intramolecular Charge Transfer ◽  
Aggregation Kinetics ◽  
Amyloid Formation ◽  
Cellular Internalization ◽  
Protein Fibrils ◽  
Model Protein ◽  
Low Toxicity ◽  
Kinetics Of ◽  
Biological Milieu

The misfolding and aggregation of proteins leading to amyloid formation has been linked to numerous diseases, necessitating the development of tools to monitor the fibrillation process. Here we report an intramolecular charge transfer (ICT) dye, DMNDC, as an alternative to Thioflavin-T (ThT), most commonly used for monitoring amyloid fibrils. Using insulin as a model protein, we show that DMNDC efficiently detects all stages of fibril formation, namely, nucleation, elongation, and saturation. An approximately 70 nm hypsochromic shift along with a large increase in emission intensity was observed upon binding of DMNDC to protein fibrils. The aggregation kinetics of insulin remained unaffected at excess DMNDC concentration, suggesting that DMNDC does not inhibit insulin aggregation. Additionally, the efficient cellular internalization and low toxicity of DMNDC make it highly suited for sensing and imaging of amyloid fibrils in the complex biological milieu.<br>

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