Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Protein Aggregation: From Molecular Biology to Human Disease
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Protein Aggregation: From Molecular Biology to Human Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 3327

Special Issue Editor

Dr. Robert Youker

E-Mail Website
Guest Editor
Department of Biology, Western Carolina University, Cullowhee, NC, USA
Interests: cystic fibrosis; protein folding and quality control; protein trafficking; chaperones
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Cells have evolved multiple pathways to control the synthesis, folding, and degradation of proteins. These pathways contain thousands of components and are collectively called the proteostasis network (PN). The PN balances the synthesis and degradation of proteins to prevent the buildup of toxic protein aggregates in the cell. It is recognized that a disruption in the PN leads to a variety of human diseases such as neuromuscular and neurodegenerative disorders, cancers, and diabetes. Important pathways that contribute to the PN include ribosomal translation, the ubiquitin–proteasome system, the unfolded protein response, autophagy, and the heat shock response. Recent data from multiple studies suggest that the robustness of the PN varies depending on the cell and tissue type, and the activity of the PN appears to decline with age. Numerous molecular, cellular, and computational studies have revealed the basic molecular components of the PN, but there is a great deal still unresolved concerning the regulation and decline of PN activity with age or human disease. This Special Issue aims to showcase original research articles, reviews, mini-reviews, and commentaries describing research advancements on the regulation of the PN molecular mechanisms involved in the prevention or clearance of protein aggregates in health, disease, and aging.

Dr. Robert Youker
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 submissions that pass pre-check are 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

  • proteinopathies
  • aggregates
  • misfolding
  • proteostatis network
  • autophagy
  • protein quality control
  • unfolded protein response (UPR)
  • ubiquitin proteasome system (UPS)
  • heat shock response (HSR)
  • er-associated degradation pathway (ERAD)
  • molecular chaperones

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

21 pages, 4734 KiB  
Article
HspB5 Chaperone Structure and Activity Are Modulated by Chemical-Scale Interactions in the ACD Dimer Interface
by Chenwei Wang, Lilong Teng, Zhiyan Silvia Liu, Aichurok Kamalova and Kathryn A. McMenimen
Int. J. Mol. Sci. 2024, 25(1), 471; https://doi.org/10.3390/ijms25010471 - 29 Dec 2023
Viewed by 657
Abstract
Small heat shock proteins (sHsps) are a family of ATP-independent molecular chaperones that function as “holdases” and prevent protein aggregation due to changes in temperature, pH, or oxidation state. sHsps have a conserved α-crystallin domain (ACD), which forms the dimer building block, flanked [...] Read more.
Small heat shock proteins (sHsps) are a family of ATP-independent molecular chaperones that function as “holdases” and prevent protein aggregation due to changes in temperature, pH, or oxidation state. sHsps have a conserved α-crystallin domain (ACD), which forms the dimer building block, flanked by variable N- and C-terminal regions. sHsps populate various oligomeric states as a function of their sequestrase activity, and these dynamic structural features allow the proteins to interact with a plethora of cellular substrates. However, the molecular mechanisms of their dynamic conformational assembly and the interactions with various substrates remains unclear. Therefore, it is important to gain insight into the underlying physicochemical properties that influence sHsp structure in an effort to understand their mechanism(s) of action. We evaluated several disease-relevant mutations, D109A, F113Y, R116C, R120G, and R120C, in the ACD of HspB5 for changes to in vitro chaperone activity relative to that of wildtype. Structural characteristics were also evaluated by ANS fluorescence and CD spectroscopy. Our results indicated that mutation Y113F is an efficient holdase, while D109A and R120G, which are found in patients with myofibrillar myopathy and cataracts, respectively, exhibit a large reduction in holdase activity in a chaperone-like light-scattering assay, which indicated alterations in substrate–sHsp interactions. The extent of the reductions in chaperone activities are different among the mutants and specific to the substrate protein, suggesting that while sHsps are able to interact with many substrates, specific interactions provide selectivity for some substrates compared to others. This work is consistent with a model for chaperone activity where key electrostatic interactions in the sHsp dimer provide structural stability and influence both higher-order sHsp interactions and facilitate interactions with substrate proteins that define chaperone holdase activity. Full article
(This article belongs to the Special Issue Protein Aggregation: From Molecular Biology to Human Disease)
►▼ Show Figures

Figure 1

18 pages, 1820 KiB  
Article
Change in the Kinetic Regime of Aggregation of Yeast Alcohol Dehydrogenase in the Presence of 2-Hydroxypropyl-β-cyclodextrin
by Vera A. Borzova, Andrey M. Chernikov, Valeriya V. Mikhaylova and Boris I. Kurganov
Int. J. Mol. Sci. 2023, 24(22), 16140; https://doi.org/10.3390/ijms242216140 - 9 Nov 2023
Viewed by 784
Abstract
Chemical chaperones are low-molecular-weight compounds that suppress protein aggregation. They can influence different stages of the aggregation process—the stage of protein denaturation, the nucleation stage and the stage of aggregate growth—and this may lead to a change in the aggregation kinetic regime. Here, [...] Read more.
Chemical chaperones are low-molecular-weight compounds that suppress protein aggregation. They can influence different stages of the aggregation process—the stage of protein denaturation, the nucleation stage and the stage of aggregate growth—and this may lead to a change in the aggregation kinetic regime. Here, the possibility of changing the kinetic regime in the presence of a chemical chaperone 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) was investigated for a test system based on the thermally induced aggregation of yeast alcohol dehydrogenase (yADH) at 56 °C. According to differential scanning calorimetry data, 2-HP-β-CD did not affect the stage of the protein molecule unfolding. Dynamic light scattering data indicated changes in the aggregation kinetics of yADH during the nucleation and aggregate growth stages in the presence of the chaperone. The analysis of kinetic curves showed that the order of aggregation with respect to protein (nc), calculated for the stage of aggregate growth, changed from nc = 1 to nc = 2 with the addition of 100 mM 2-HP-β-CD. The mechanism of 2-HP-β-CD action on the yADH thermal aggregation leading to a change in its kinetic regime of aggregation is discussed. Full article
(This article belongs to the Special Issue Protein Aggregation: From Molecular Biology to Human Disease)
►▼ Show Figures

Figure 1

8 pages, 1640 KiB  
Article
Cue to Acid-Induced Long-Range Conformational Changes in an Antibody Preceding Aggregation: The Structural Origins of the Subpeaks in Kratky Plots of Small-Angle X-ray Scattering
by Hiroshi Imamura and Shinya Honda
Int. J. Mol. Sci. 2023, 24(15), 12042; https://doi.org/10.3390/ijms241512042 - 27 Jul 2023
Viewed by 1098
Abstract
Antibody aggregation, followed by acid denaturation and neutralization of pH, is one of the reasons why the production of therapeutic monoclonal antibodies (mAbs) is expensive. Determining the structural details of acid-denatured antibodies is important for understanding their aggregation mechanism and for antibody engineering. [...] Read more.
Antibody aggregation, followed by acid denaturation and neutralization of pH, is one of the reasons why the production of therapeutic monoclonal antibodies (mAbs) is expensive. Determining the structural details of acid-denatured antibodies is important for understanding their aggregation mechanism and for antibody engineering. Recent research has shown that monoclonal antibodies of human/humanized immunoglobulin G1 (IgG1) become smaller globules at pH 2 compared to their native structure at pH 7. This acid-denatured species is unstable at pH 7 and prone to aggregation by neutralization of pH. Small-angle X-ray scattering (SAXS) data have revealed an acid-induced reduction in the subpeaks in Kratky plot, indicating conformational changes that can lead to aggregation. The subpeaks are well resolved at pH > 3 but less pronounced at pH ≤ 2. One of the weakened subpeaks indicates loosely organized inter-region (Fab-Fab and Fab-Fc) correlations due to acid denaturation. However, the structural origin of the other subpeak (called q3 peak in this study) has not been established because its q region could represent the various inter-region, inter-domain, and intra-domain correlations in IgG1. In this study, we aimed to untangle the effects of domain–domain correlations on Kratky’s q3 peak based on the computed SAXS of the crystal structure of IgG1. The q3 peak appeared in the static structure and was more prominent in the Fc region than in the Fab or isolated domains. Further brute-force analysis indicated that longer domain–domain correlations, including the inter-region, also positively contribute to Kratky’s q3 peak. Thus, the distortion of the Fc region and a longer inter-region correlation initiate acid denaturation and aggregation. Full article
(This article belongs to the Special Issue Protein Aggregation: From Molecular Biology to Human Disease)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop