Abstract
Prions are a novel class of infectious pathogens that cause a group of fatal prion diseases in which the benign cellular form of the prion protein (PrP C) is transformed into the disease-related scrapie variant (PrP SC). The two PrP isoforms differ in their structure and resistance to degradation. The molecular mechanism by which the PrP SC is formed and causes infectivity or neurodegeneration is not known. In a compelling and emerging view, posttranslational modifications (or the lack thereof) play roles in the transformation of PrP C to PrP SC. Human PrP contains two consensus sites for N-linked glycosylation, at Asn181 and Asn197. From the functional standpoint, glycosylation can modify either the conformation of PrP C, or the stability of PrPSC and, hence, the rate of PrPSC clearance. So far the NMR structures of only recombinant, non-glycosylated prions are known, while the structure of the glycosylated form is estimated by molecular modeling. A number of native amino acid mutations in PrP can be mapped near the glycosylation sites. Normal prion protein has been demonstrated to be a copper binding protein, and increasing evidence has shown correlation between the level of PrP expression and tolerance to oxidative stress. Moreover, histochemistry for nitrotyrosine is used for detection of neuronal labeling, a sign of a peroxynitrite-mediated neuronal degradation and a marker for nitrative stress in scrapie-infected mouse brains. It is an intriguing proposition that the post translational modifications alone, or in combination with amino acid changes, play dominant roles in the pathogenic transformation of PrPC to PrPSC.
Keywords: Post-Translational, Prion Proteins, GLYCOSYLATION, ASPARAGINE, encephalopathy, Creutzfeldt-Jacob disease, Glycosyl-phosphatidyl-inositol, Sodium dodecyl, Superoxide dismutase
Current Protein & Peptide Science
Title: Post-Translational Modifications in Prion Proteins
Volume: 3 Issue: 6
Author(s): Laszlo Otvos, Jr. and Mare Cudic
Affiliation:
Keywords: Post-Translational, Prion Proteins, GLYCOSYLATION, ASPARAGINE, encephalopathy, Creutzfeldt-Jacob disease, Glycosyl-phosphatidyl-inositol, Sodium dodecyl, Superoxide dismutase
Abstract: Prions are a novel class of infectious pathogens that cause a group of fatal prion diseases in which the benign cellular form of the prion protein (PrP C) is transformed into the disease-related scrapie variant (PrP SC). The two PrP isoforms differ in their structure and resistance to degradation. The molecular mechanism by which the PrP SC is formed and causes infectivity or neurodegeneration is not known. In a compelling and emerging view, posttranslational modifications (or the lack thereof) play roles in the transformation of PrP C to PrP SC. Human PrP contains two consensus sites for N-linked glycosylation, at Asn181 and Asn197. From the functional standpoint, glycosylation can modify either the conformation of PrP C, or the stability of PrPSC and, hence, the rate of PrPSC clearance. So far the NMR structures of only recombinant, non-glycosylated prions are known, while the structure of the glycosylated form is estimated by molecular modeling. A number of native amino acid mutations in PrP can be mapped near the glycosylation sites. Normal prion protein has been demonstrated to be a copper binding protein, and increasing evidence has shown correlation between the level of PrP expression and tolerance to oxidative stress. Moreover, histochemistry for nitrotyrosine is used for detection of neuronal labeling, a sign of a peroxynitrite-mediated neuronal degradation and a marker for nitrative stress in scrapie-infected mouse brains. It is an intriguing proposition that the post translational modifications alone, or in combination with amino acid changes, play dominant roles in the pathogenic transformation of PrPC to PrPSC.
Export Options
About this article
Cite this article as:
Otvos, Jr. Laszlo and Cudic Mare, Post-Translational Modifications in Prion Proteins, Current Protein & Peptide Science 2002; 3 (6) . https://dx.doi.org/10.2174/1389203023380440
DOI https://dx.doi.org/10.2174/1389203023380440 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
Valproic Acid Attenuates Neuronal Loss in the Brain of APP/PS1 Double Transgenic Alzheimer’s Disease Mice Model
Current Alzheimer Research Editorial: Novel Perspectives in the Treatment of Epilepsy
Current Pharmaceutical Design Natural Products Based Ayurvedic Formulations: Chemical Cons tituents and Treatment in Neurodegenerative Disordersǂ
Mini-Reviews in Organic Chemistry Sphingosine-1-Phosphate Receptors in the Central Nervous and Immune Systems
Current Drug Targets Chemokines as Potential Therapeutic Targets in Atherosclerosis
Current Drug Targets Caring for HIV-Infected Patients in the ICU in The Highly Active Antiretroviral Therapy Era
Current HIV Research Cerebral Microinfarcts and Dementia: A Systematic Review and Metaanalysis
Current Alzheimer Research Antioxidants as a Potential Therapy Against Age-Related Neurodegenerative Diseases: Amyloid Beta Toxicity and Alzheimers Disease
Current Pharmaceutical Design Informal Caregiving for People with Dementia and Women’s Health: A Gender-based Assessment of Studies on Resilience
Current Women`s Health Reviews CHF5074 Reduces Biomarkers of Neuroinflammation in Patients with Mild Cognitive Impairment: A 12-Week, Double-Blind, Placebo- Controlled Study
Current Alzheimer Research Recent Advances in the Discovery of α1-Adrenoceptor Agonists
Current Topics in Medicinal Chemistry The Potential Role of Glycogen Synthase Kinase 3 Inhibitors as Amyotrophic Lateral Sclerosis Pharmacological Therapy
Current Medicinal Chemistry The Vascular Component of Alzheimer`s Disease
Current Neurovascular Research Meet Our Editorial Board Member:
Current Drug Safety Patent Selections
Recent Patents on Biomarkers Catalpol: A Potential Therapeutic for Neurodegenerative Diseases
Current Medicinal Chemistry Treating High Density Lipoprotein Cholesterol (HDL-C): Quantity Versus Quality
Current Pharmaceutical Design The Role of Lipids and Membranes in the Pathogenesis of Alzheimer's Disease: A Comprehensive View
Current Alzheimer Research Safety of Systemic Biologic Agents in the Treatment of Non-malignant Skin Disorders
Current Drug Safety Editorial
Recent Patents on CNS Drug Discovery (Discontinued)