Abstract
Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders associated with the conformational conversion of the cellular prion protein, PrPC, into a pathological form known as prion or PrPSc. They can be classified into sporadic, inherited and infectious forms. Spontaneous generation of PrPSc in inherited forms of prion diseases is caused by mutations in the human prion protein gene (PRNP). A major goal in prion biology is unraveling the molecular mechanism by which PrPC misfolds and leads to development of diseases. Structural characterization of various human PrP (HuPrP) variants may be helpful for better understanding of the earliest stages of the conformational changes leading to spontaneous generation of prions. Here, we review the results of the recent high-resolution nuclear magnetic resonance (NMR) structural studies on HuPrPs with pathological Q212P and V210I mutations linked with Gerstmann-Sträussler-Scheinker (GSS) syndrome and familial Creutzfeldt-Jakob disease (fCJD), respectively, and HuPrP carrying naturally occurring E219K polymorphism considered to protect against sporadic CJD (sCJD). We describe subtle local differences between the three-dimensional (3D) structures of HuPrP mutants and the wild-type (WT) protein, providing new insights into the possible key structural determinants underlying conversion of PrPC into PrPSc. Also highlighted are the most recent findings from NMR studies about the effect of pH on the structural features of HuPrP with V210I mutation.
Keywords: Mutant, NMR structure, pH, prion protein, protective polymorphism, transmissible spongiform encephalopathy.
Current Topics in Medicinal Chemistry
Title:NMR Structural Studies of Human Cellular Prion Proteins
Volume: 13 Issue: 19
Author(s): Ivana Biljan, Gregor Ilc, Gabriele Giachin, Giuseppe Legname and Janez Plavec
Affiliation:
Keywords: Mutant, NMR structure, pH, prion protein, protective polymorphism, transmissible spongiform encephalopathy.
Abstract: Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders associated with the conformational conversion of the cellular prion protein, PrPC, into a pathological form known as prion or PrPSc. They can be classified into sporadic, inherited and infectious forms. Spontaneous generation of PrPSc in inherited forms of prion diseases is caused by mutations in the human prion protein gene (PRNP). A major goal in prion biology is unraveling the molecular mechanism by which PrPC misfolds and leads to development of diseases. Structural characterization of various human PrP (HuPrP) variants may be helpful for better understanding of the earliest stages of the conformational changes leading to spontaneous generation of prions. Here, we review the results of the recent high-resolution nuclear magnetic resonance (NMR) structural studies on HuPrPs with pathological Q212P and V210I mutations linked with Gerstmann-Sträussler-Scheinker (GSS) syndrome and familial Creutzfeldt-Jakob disease (fCJD), respectively, and HuPrP carrying naturally occurring E219K polymorphism considered to protect against sporadic CJD (sCJD). We describe subtle local differences between the three-dimensional (3D) structures of HuPrP mutants and the wild-type (WT) protein, providing new insights into the possible key structural determinants underlying conversion of PrPC into PrPSc. Also highlighted are the most recent findings from NMR studies about the effect of pH on the structural features of HuPrP with V210I mutation.
Export Options
About this article
Cite this article as:
Biljan Ivana, Ilc Gregor, Giachin Gabriele, Legname Giuseppe and Plavec Janez, NMR Structural Studies of Human Cellular Prion Proteins, Current Topics in Medicinal Chemistry 2013; 13 (19) . https://dx.doi.org/10.2174/15680266113136660169
DOI https://dx.doi.org/10.2174/15680266113136660169 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Biological Targets of Antitumor Indolocarbazoles Bearing a Sugar Moiety
Current Medicinal Chemistry - Anti-Cancer Agents Editorial (Hot Topic: Innovative Approaches for the Management of Pediatric Malignancies)
Current Medicinal Chemistry Exploiting Internal Ribosome Entry Sites in Gene Therapy Vector Design
Current Gene Therapy Inhibitor at the Gates, Inhibitor in the Chamber: Allosteric and Competitive Inhibitors of the Proteasome as Prospective Drugs
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Natural Products as Anticancer Agents
Current Drug Targets Thrombospondin and Apoptosis: Molecular Mechanisms and Use for Design of Complementation Treatments
Current Drug Targets Inhibitory Effect of Ebselen on Cerebral Acetylcholinesterase Activity In Vitro: Kinetics and Reversibility of Inhibition
Current Pharmaceutical Design Cannabis-Derived Substances in Cancer Therapy – An Emerging Anti- Inflammatory Role for the Cannabinoids
Current Clinical Pharmacology Sinonasal Carcinoma: Updated Phenotypic and Molecular Characterization
Current Cancer Therapy Reviews Induced Pluripotent Stem Cell-Based Studies of Parkinson's Disease: Challenges and Promises
CNS & Neurological Disorders - Drug Targets Thymoquinone Anticancer Discovery: Possible Mechanisms
Current Drug Discovery Technologies Signaling Mechanisms Underlying Aβ Toxicity: Potential Therapeutic Targets for Alzheimers Disease
CNS & Neurological Disorders - Drug Targets Sevoflurane But Not Propofol Provided Dual Effects of Cell Survival in Human Neuroblastoma SH-SY5Y Cells
Current Alzheimer Research The Effect of Lipoic Acid on Macro and Trace Metal Levels in Living Tissues Exposed to Oxidative Stress
Anti-Cancer Agents in Medicinal Chemistry Current Management of Neonatal Liver Tumors
Current Pediatric Reviews The 18 kDa Translocator Protein (TSPO): A New Perspective in Mitochondrial Biology
Current Molecular Medicine Comparison of Glucocorticoid Receptor- and Epigenetically Regulated Genes in Proliferating Versus Growth-Arrested Neuro-2a Cells
CNS & Neurological Disorders - Drug Targets Role of Flavonoids in Future Anticancer Therapy by Eliminating the Cancer Stem Cells
Current Stem Cell Research & Therapy Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43
Current Neuropharmacology [11C]Meta-Hydroxyephedrine PET/CT
Current Radiopharmaceuticals