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
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
- 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
-
Cell Survival Signaling in Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry Monoclonal Antibodies, Small Molecule Inhibitors and Antibody-drug Conjugates as HER2 Inhibitors
Current Medicinal Chemistry Evaluation of Anticancer, Antibacterial and Antioxidant Properties of a Medicinally Treasured Fern Tectaria coadunata with its Phytoconstituents Analysis by HR-LCMS
Anti-Cancer Agents in Medicinal Chemistry Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin
Current Cancer Drug Targets Editorial (Hot Topic: Innovative Approaches for the Management of Pediatric Malignancies)
Current Medicinal Chemistry Functional Interactions of Tau and their Relevance for Alzheimers Disease
Current Alzheimer Research Emerging β-Amyloid Therapies for the Treatment of Alzheimers Disease
Current Pharmaceutical Design Type 2 Diabetes Mellitus and Alzheimer’s Disease: Bridging the Pathophysiology and Management
Current Pharmaceutical Design Protein Kinase C Pharmacology: Perspectives on Therapeutic Potentials as Antidementic and Cognitive Agents
Recent Patents on CNS Drug Discovery (Discontinued) Neuronal Acetylcholine Nicotinic Receptors as New Targets for Lung Cancer Treatment
Current Pharmaceutical Design Xanthan Gum Coated Mucoadhesive Liposomes for Efficient Nose to Brain Delivery of Curcumin
Drug Delivery Letters EGFR Transactivation by Peptide G Protein-Coupled Receptors in Cancer
Current Drug Targets Current Evidence and Potential Mechanisms of Therapeutic Action of PEDF in Cervical Cancer Treatment
Current Molecular Medicine Cdc25A Protein Phosphatase: A Therapeutic Target for Liver Cancer Therapies
Anti-Cancer Agents in Medicinal Chemistry Bispecific Antibodies: An Innovative Arsenal to Hunt, Grab and Destroy Cancer Cells
Current Pharmaceutical Biotechnology Modulation of intracellular pH in human ovarian cancer.
Current Molecular Medicine Cancer Stem Cells and their Management in Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Evaluation of Vitamin C as a Personalized Adjuvant Medicine: Pharmacogenomic Studies
Current Pharmacogenomics and Personalized Medicine The Adenine Nucleotide Translocator: A New Potential Chemotherapeutic Target
Current Drug Targets Role of Acetylcholinesterase Inhibitors in the Metabolism of Amyloid Precursor Protein
Current Drug Targets - CNS & Neurological Disorders