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
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
-
Relations between Sensorimotor Integration and Speech Disorders in Parkinson's Disease
Current Alzheimer Research Protein Conformational Pathology in Alzheimers and Other Neurodegenerative Diseases; New Targets for Therapy
Current Alzheimer Research Biomarkers for Alzheimer’s Disease
Current Alzheimer Research Erratum
Current Alzheimer Research Recent Software Developments and Applications in Functional Imaging
Current Pharmaceutical Biotechnology Structural MRI Biomarkers of Mild Cognitive Impairment from Young Elders to Centenarians
Current Alzheimer Research Anti-Inflammatory Drugs in Psychiatry
Inflammation & Allergy - Drug Targets (Discontinued) Recent Advances in the Treatment of Amyotrophic Lateral Sclerosis. Emphasis on Kynurenine Pathway Inhibitors
Central Nervous System Agents in Medicinal Chemistry Subject Index to Volume 2
Current Vascular Pharmacology Tualang Honey and its Methanolic Fraction Improve LPS-induced Learning and Memory Impairment in Male Rats: Comparison with Memantine
Current Nutrition & Food Science Toxics of Tobacco Smoke and Cardiovascular System: From Functional to Cellular Damage
Current Pharmaceutical Design Is Nitric Oxide Assuming a Janus-Face in The Central Nervous System?
Current Medicinal Chemistry Gender and Cardiovascular Mortality in Northern and Southern European Populations
Current Pharmaceutical Design Drug Transport Across the Blood-Brain Barrier and the Impact of Breast Cancer Resistance Protein (ABCG2)
Current Topics in Medicinal Chemistry The Brain Protective Effect of rTMS (Repetitive Transcranial Magnetic Stimulation) in Depression: A Mini-Review in Animal Studies
Medicinal Chemistry Immune Functions of Glia and Neurons in the Central Nervous System
Current Immunology Reviews (Discontinued) High Doses of In vitro Beta-carotene, Alpha-Tocopherol and Ascorbic Acid Induce Oxidative Stress and Secretion of IL-6 in Peripheral Blood Mononuclear Cells from Healthy Donors
Current Aging Science Patent Selections:
Recent Patents on CNS Drug Discovery (Discontinued) Zoledronic Acid Use and Risk of Cognitive Decline among Elderly Women and Men with Osteoporosis
Endocrine, Metabolic & Immune Disorders - Drug Targets Neuroimaging Correlates of 22q11.2 Deletion Syndrome: Implications for Schizophrenia Research
Current Topics in Medicinal Chemistry