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Biomolecules
Special Issues
The Role of Scaffold Proteins in Human Diseases
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The Role of Scaffold Proteins in Human Diseases

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 3496

Special Issue Editors

Prof. Dr. László Buday

E-Mail Website
Guest Editor
Institute of Molecular Life Sciences, HUN-REN Research Centre of Natural Sciences, 1117 Budapest, Hungary
Interests: cell signalling; tyrosine kinases; scaffold proteins; SH2 and SH3 domains; Ras signalling
Dr. Virag Vas

E-Mail Website
Guest Editor
Institute of Molecular Life Sciences, HUN-REN Research Centre of Natural Sciences, Budapest, Hungary
Interests: cell communication; signal transduction; disease models; cancer cell biology; cancer evolution; EGFR signalling; metastasis formation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Scaffold proteins play a crucial role in the organization and regulation of cellular signalling pathways. They act as molecular platforms that bring together various signalling molecules, facilitating their interaction and coordination. The significance of scaffold proteins in human diseases is vast, as they can influence the development, progression, and treatment of various conditions. Understanding the role of scaffold proteins in different cellular processes is essential for unravelling the molecular mechanisms underlying human diseases, such as cancer progression, neurological disorders, immune system regulation, cardiovascular diseases, and metabolic disorders. Targeting scaffold proteins or their associated signalling pathways may offer new therapeutic strategies for the treatment of various disorders. However, it is important to note that proteomic/epigenomic/genomic research in this field is ongoing, and our understanding of scaffold proteins and their implications in human diseases continues to evolve.

In this Special Issue of Biomolecules, we will provide an open access platform for reviews and original research papers describing all aspects of research on scaffold proteins in human diseases.

Prof. Dr. László Buday
Dr. Virag Vas
Guest Editors

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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • scaffold proteins
  • cellular signalling
  • protein–protein interactions
  • protein domains
  • human diseases
  • drug targets
  • protein complex formation
  • pathogenic alterations

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Published Papers (2 papers)

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Research

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21 pages, 5025 KiB  
Article
Targeting Grb2 SH3 Domains with Affimer Proteins Provides Novel Insights into Ras Signalling Modulation
by Anna A. S. Tang, Andrew Macdonald, Michael J. McPherson and Darren C. Tomlinson
Biomolecules 2024, 14(8), 1040; https://doi.org/10.3390/biom14081040 - 22 Aug 2024
Cited by 1 | Viewed by 2006
Abstract
Src homology 3 (SH3) domains play a critical role in mediating protein–protein interactions (PPIs) involved in cell proliferation, migration, and the cytoskeleton. Despite their abundance in the human proteome, the functions and molecular interactions of many SH3 domains remain unknown, and this is [...] Read more.
Src homology 3 (SH3) domains play a critical role in mediating protein–protein interactions (PPIs) involved in cell proliferation, migration, and the cytoskeleton. Despite their abundance in the human proteome, the functions and molecular interactions of many SH3 domains remain unknown, and this is in part due to the lack of SH3-domain-specific reagents available for their study. Affimer proteins have been developed as affinity reagents targeting a diverse range of targets, including those involved in PPIs. In this study, Affimer proteins were isolated against both the N- and C-terminal SH3 domains (NSH3 and CSH3) of growth-factor-receptor-bound protein 2 (Grb2), an adapter protein that provides a critical link between cell surface receptors and Ras signalling pathways. Targeting the CSH3 alone for the inhibition of PPIs appeared sufficient for curtailing Ras signalling in mammalian cell lines stimulated with human epidermal growth factor (EGF), which conflicts with the notion that the predominant interactions with Ras activating Son of sevenless (SOS) occur via the NSH3 domain. This result supports a model in which allosteric mechanisms involved in Grb2-SOS1 interaction modulate Ras activation. Full article
(This article belongs to the Special Issue The Role of Scaffold Proteins in Human Diseases)
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Review

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25 pages, 321 KiB  
Review
Scaffold Proteins in Fibrotic Diseases of Visceral Organs
by Piaopiao Sun, Liliang Yang, Keqing Yu, Jing Wang and Jie Chao
Biomolecules 2025, 15(3), 420; https://doi.org/10.3390/biom15030420 - 16 Mar 2025
Viewed by 789
Abstract
Fibrosis, characterized by excessive extracellular matrix (ECM) deposition, disrupts tissue architecture and impairs organ function, ultimately leading to severe health consequences and even failure of vital organs such as the lung, heart, liver, and kidney. Despite significant advances in understanding the molecular mechanisms [...] Read more.
Fibrosis, characterized by excessive extracellular matrix (ECM) deposition, disrupts tissue architecture and impairs organ function, ultimately leading to severe health consequences and even failure of vital organs such as the lung, heart, liver, and kidney. Despite significant advances in understanding the molecular mechanisms underlying fibrosis, effective therapeutic options remain limited. Emerging evidence highlights scaffold proteins as critical regulators in the progression of fibrosis. These multifunctional proteins serve as molecular platforms that organize and coordinate key signaling pathways—including those governing ECM remodeling, cytoskeletal organization, and cell migration—thereby integrating both profibrotic and antifibrotic signals. Their pivotal role in linking mechanotransduction, inflammatory, and developmental signals offers a unique therapeutic window, as targeted interventions (e.g., small-molecule inhibitors, peptides, biologics, and gene therapy) are emerging to modulate these pathways. This review synthesizes recent findings on scaffold protein functions across multiple organs and discusses novel therapeutic strategies to manage and potentially reverse fibrosis. Full article
(This article belongs to the Special Issue The Role of Scaffold Proteins in Human Diseases)
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