Abstract
Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation, which shares many structural properties with the pre-molten globule state, a partially folded intermediate first found during the equilibrium and kinetic (un)folding studies of several globular proteins and later described as one of the structural forms of natively unfolded proteins. The flexibility of this structural form is essential for the conformational rearrangements driving the formation of the core cross-beta structure of the amyloid fibril. Obviously, molecular mechanisms describing amyloidogenesis of ordered and natively unfolded proteins are different. For ordered protein to fibrillate, its unique and rigid structure has to be destabilized and partially unfolded. On the other hand, fibrillogenesis of a natively unfolded protein involves the formation of partially folded conformation; i.e., partial folding rather than unfolding. In this review recent findings are surveyed to illustrate some unique features of the natively unfolded proteins amyloidogenesis.
Keywords: Amyloid fibril, fibrillation, amyloidogenesis, conformational disease, partially folded conformation, natively unfolded protein, intrinsically disordered protein
Current Alzheimer Research
Title: Amyloidogenesis of Natively Unfolded Proteins
Volume: 5 Issue: 3
Author(s): Vladimir N. Uversky
Affiliation:
Keywords: Amyloid fibril, fibrillation, amyloidogenesis, conformational disease, partially folded conformation, natively unfolded protein, intrinsically disordered protein
Abstract: Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation, which shares many structural properties with the pre-molten globule state, a partially folded intermediate first found during the equilibrium and kinetic (un)folding studies of several globular proteins and later described as one of the structural forms of natively unfolded proteins. The flexibility of this structural form is essential for the conformational rearrangements driving the formation of the core cross-beta structure of the amyloid fibril. Obviously, molecular mechanisms describing amyloidogenesis of ordered and natively unfolded proteins are different. For ordered protein to fibrillate, its unique and rigid structure has to be destabilized and partially unfolded. On the other hand, fibrillogenesis of a natively unfolded protein involves the formation of partially folded conformation; i.e., partial folding rather than unfolding. In this review recent findings are surveyed to illustrate some unique features of the natively unfolded proteins amyloidogenesis.
Export Options
About this article
Cite this article as:
Uversky N. Vladimir, Amyloidogenesis of Natively Unfolded Proteins, Current Alzheimer Research 2008; 5 (3) . https://dx.doi.org/10.2174/156720508784533312
DOI https://dx.doi.org/10.2174/156720508784533312 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
TP73, An Under-Appreciated Player in Non-Hodgkin Lymphoma Pathogenesis and Management
Current Molecular Medicine Interferon-Alpha in the Treatment of Philadelphia-Negative Chronic Myeloproliferative Neoplasms. Status and Perspectives
Current Drug Targets High Content, Multi-Parameter Analyses in Buccal Cells to Identify Alzheimer’s Disease
Current Alzheimer Research Hydroxamic Acids, Recent Breakthroughs in Stereoselective Synthesis and Biological Evaluations
Current Organic Synthesis Clinical Evidence of Herb-Drug Interactions: A Systematic Review by the Natural Standard Research Collaboration
Current Drug Metabolism Anti-Angiogenic Treatment for Exudative Age-Related Macular Degeneration: New Strategies are Underway
Current Angiogenesis (Discontinued) Pyridine Based Antitumour Compounds Acting at the Colchicine Site
Current Medicinal Chemistry Peroxisome Proliferator-Activated Receptors: Role of Isoform Gamma in the Antineoplastic Effect of Iodine in Mammary Cancer
Current Cancer Drug Targets P2X Receptors and Inflammation
Current Medicinal Chemistry The Proteasome in Health and Disease
Current Pharmaceutical Design Retinoids in Cancer Chemoprevention
Current Cancer Drug Targets New Hybrid Scaffolds Based on Carbazole-Chalcones as Potent Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Fighting Fire with Fire: A Patent for the Combined Application of Oncolytic Herpes Viruses and Antiangiogenic Agents in the Battle Against Human Cancers
Recent Patents on Anti-Cancer Drug Discovery An Updated Organic Classification of Tyrosinase Inhibitors on Melanin Biosynthesis
Current Organic Chemistry Patent Selections:
Recent Patents on Drug Delivery & Formulation Raf Inhibitors as Therapeutic Agents Against Neurodegenerative Diseases
CNS & Neurological Disorders - Drug Targets Why Multiples of 21? Why does Selenoprotein P Contain Multiple Selenocysteine Residues?
Current Nutraceuticals B Lymphocytes, Potent Antigen Presenting Cells for Preferential Expansion of Allo-Reactive FoxP3+ CD4 Regulatory T Cells
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Leptin Plasma Levels in the General Population: Influence of Age, Gender, Body Weight and Medical History
Protein & Peptide Letters UGT1A1 Mediated Drug Interactions and its Clinical Relevance
Current Drug Metabolism