ijms-logo

Journal Browser

Journal Browser

Special Issue "Regulation of Functional Protein Aggregation: From Amyloids to Biomaterials"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 30 June 2021.

Special Issue Editors

Prof. Dr. J.B. Bernd Helms
E-Mail Website
Guest Editor
Department of Biomolecular Health Sciences, Utrecht University, Utrecht, The Netherlands
Interests: membrane transport; lipids; lipid droplets; lipidomics; liver fibrosis; liver regeneration; hepatic stellate cells; retinoids; functional amyloids; CAP superfamily proteins
Dr. Dora V. Kaloyanova
E-Mail
Guest Editor
Utrecht University, Department of Biomolecular Health Sciences, Utrecht, Netherlands.
Interests: protein-protein interactions; protein aggregation; autophagy; reproduction
Dr. Stefan Rüdiger
E-Mail
Guest Editor
Utrecht University, Department of Chemistry, Utrecht, Netherlands
Interests: protein folding and Aggregation; Tau; heat shock proteins; chaperones

Special Issue Information

Dear Colleagues,

Numerous proteins and peptides have the capacity to self‐assemble into amyloid fibrils that are characterized by β-sheet polymer structures. Amyloid assembly has long been associated with many devastating human diseases, such as Alzheimer’s, Parkinson’s, diabetes type 2, and ALS.

Strikingly, amyloid folds with their remarkable, multifaceted appearance are also present in nature and occurring in various physiologically forms as so-called “functional amyloids”. They appear in fungi, insects, archaea, bacteria, and humans. Functional amyloids are often characterized by their reversible nature, unlike the extremely stable pathological amyloid fibrils. In addition, their presence requires careful biophysical control to avoid potentially harmful effects. This strongly suggests that functional amyloid assemblies are subject to strict regulation, leading to the formation of correct ‘sub’-structures to prevent toxicity and allowing reversal of amyloid assembly. Likewise, amyloid formation may be linked to liquid–liquid phase separation. The concept that is emerging is that amyloidic β-sheet folds can perform a multitude of biological functions. Rapid progress in the field of protein amyloid assembly now offers highly exciting new opportunities to unravel the secrets of amyloid formation. This will not only benefit the understanding of the role of functional and pathological amyloids in health and disease but will also promote innovation in bioengineering. The unique chemical characteristics of amyloidogenic proteins can be used to develop brand new materials for biofilm, biosensor, bioelectronic, and biomedical applications.

This Special Issue calls for original research in basic science and translational research, as well as for reviews and perspectives that address the existence, regulation, and role of functional amyloids in the physiology of organisms. In addition, contributions that describe progress to create new biomaterials based on β-sheet assemblies are welcomed.

Prof. Dr. J.B. Helms, 

Dr. Dora V. Kaloyanova

Dr. Stefan Rüdiger

Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Protein aggregation
  • β-sheet fold
  • Amyloids
  • Protein fibrils
  • Functional amyloids
  • Bioengineering
  • Biomaterials

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation
Int. J. Mol. Sci. 2021, 22(6), 2888; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062888 - 12 Mar 2021
Viewed by 349
Abstract
Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, [...] Read more.
Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease. Full article
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins
Int. J. Mol. Sci. 2020, 21(18), 6530; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186530 - 07 Sep 2020
Cited by 2 | Viewed by 650
Abstract
The idea that amyloid fibrils and other types of protein aggregates are toxic for cells has been challenged by the discovery of a variety of functional aggregates. However, an identification of crucial differences between pathological and functional aggregation remains to be explored. Functional [...] Read more.
The idea that amyloid fibrils and other types of protein aggregates are toxic for cells has been challenged by the discovery of a variety of functional aggregates. However, an identification of crucial differences between pathological and functional aggregation remains to be explored. Functional protein aggregation is often reversible by nature in order to respond properly to changing physiological conditions of the cell. In addition, increasing evidence indicates that fast fibril growth is a feature of functional amyloids, providing protection against the long-term existence of potentially toxic oligomeric intermediates. It is becoming clear that functional protein aggregation is a complexly organized process that can be mediated by a multitude of biomolecular factors. In this overview, we discuss the roles of diverse biomolecules, such as lipids/membranes, glycosaminoglycans, nucleic acids and metal ions, in regulating functional protein aggregation. Our studies on the protein GAPR-1 revealed that several of these factors influence the amyloidogenic properties of this protein. These observations suggest that GAPR-1, as well as the cysteine-rich secretory proteins, antigen 5 and pathogenesis-related proteins group 1 (CAP) superfamily of proteins that it belongs to, require the assembly into an amyloid state to exert several of their functions. A better understanding of functional aggregate formation may also help in the prevention and treatment of amyloid-related diseases. Full article
Show Figures

Graphical abstract

Back to TopTop