Exploring the Structural and Functional Diversity of Proteins: Foundations of Life and Biological Complexity

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 31 May 2026 | Viewed by 768

Special Issue Editor


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Guest Editor
Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ, USA
Interests: AAA+ protein; RNA-binding protein; protein kinase; PTMs; protein structure, function, and diseases; protein and RNA homeostasis; neurodegeneration; cancer

Special Issue Information

Dear Colleagues,

Proteins are fundamental to life, with a vast array of structures and functions essential to biological processes. ATPases, such as AAA+ proteins, power cellular maintenance through substrate translocation, while RNA-binding proteins (RBPs) regulate gene expression and RNA metabolism. Protein kinases, through phosphorylation, control cell signaling pathways critical for growth and survival. These proteins exhibit a dynamic range of mechanisms revealed in recently advanced cryo-electron microscopy studies, which suggest the adaptable nature of these biomolecules. These proteins play pivotal roles in aging, neurodegeneration, and cancer, where dysregulation can lead to disease progression. Misfolded proteins in neurodegenerative disorders, overactive kinases in cancer, and cellular decline in aging highlight their significance in human health and disease. This issue explores how structural variations in proteins drive diverse functions and adaptability, crucial to life’s complexity and evolutionary innovation.

Dr. Jiabei Lin
Guest Editor

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Keywords

  • AAA+ protein
  • RNA-binding protein
  • protein kinase
  • PTMs
  • protein structure, function, and diseases
  • protein and RNA homeostasis
  • neurodegeneration
  • cancer

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Published Papers (1 paper)

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Review

21 pages, 1484 KB  
Review
In-Depth Study of Low-Complexity Domains: From Structural Diversity to Disease Mechanisms
by Haixia Xu, Kaili Zhou, Lianren Xia, Kejin Ren and Yongjie Xu
Cells 2025, 14(22), 1752; https://doi.org/10.3390/cells14221752 - 9 Nov 2025
Viewed by 410
Abstract
Low-complexity domains (LCDs) are protein regions characterized by a simple amino acid composition and low sequence complexity, as they are typically composed of repeats or a limited set of a few amino acids. Historically dismissed as “garbage sequences”, these regions are now acknowledged [...] Read more.
Low-complexity domains (LCDs) are protein regions characterized by a simple amino acid composition and low sequence complexity, as they are typically composed of repeats or a limited set of a few amino acids. Historically dismissed as “garbage sequences”, these regions are now acknowledged as critical functional elements. This review systematically explores the structural characteristics, biological functions, pathological roles, and research methodologies associated with LCDs. Structurally, LCDs are marked by intrinsic disorder and conformational dynamics, with their amino acid composition (e.g., G/Y-rich, Q-rich, S/R-rich, P-rich) dictating structural tendencies (e.g., β-sheet formation, phase separation ability). Functionally, LCDs mediate protein–protein interactions, drive liquid–liquid phase separation (LLPS) to form biomolecular condensates, and play roles in signal transduction, transcriptional regulation, cytoskeletal organization, and nuclear pore transportation. Pathologically, LCD dysfunction—such as aberrant phase separation or aggregation—is implicated in neurodegenerative diseases (e.g., ALS, AD), cancer (e.g., Ewing sarcoma), and prion diseases. We also summarize the methodological advances in LCD research, including biochemical (CD, NMR), structural (cryo-EM, HDX-MS), cellular (fluorescence microscopy), and computational (MD simulations, AI prediction) approaches. Finally, we highlight current challenges (e.g., structural heterogeneity, causal ambiguity of phase separation) and future directions (e.g., single-molecule techniques, AI-driven LCD design, targeted therapies). This review provides a comprehensive perspective on LCDs, illuminating their pivotal roles in cellular physiology and disease, and offering insights for future research and therapeutic development. Full article
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