Abstract
Until now it is still not clear which structural elements of the prion protein (PrP) are involved in its conversion process. Characterisation of these essential regions would help to understand the conversion process itself and might help to develop specific therapeutic approaches to inhibit PrPres formation by dominant inhibitory mutations. To address this important question 33 evenly spaced insertion mutants were generated spanning the entire sequence of the murine 3F4- tagged PrP. The mutants were expressed by retroviral transduction in three different scrapie infected cell lines (ScN2a; SMB[RC040]; SMB[22F]). The convertibility was affected not only by introducing the insertion in the putatively refolded region (aa100-170), but also in the C-terminus of PrP (up to aa214). Moreover, dominant inhibitory effects on conversion were observed for PrP-mutants at four distinguished regions (aa100-112; aa130-154; aa166-172, aa196-200). Computer based structural analysis revealed that these segments were organized in two structurally clearly separated regions supporting the idea that they could function as protein-protein interaction sites which are necessary during seed formation.
Keywords: PrP mutants, PrP conversion, Glycosylation and cellular trafficking, PrP seed formation
Infectious Disorders - Drug Targets
Title: Inhibition of Prion Amplification by Expression of Dominant Inhibitory Mutants - A Systematic Insertion Mutagenesis Study
Volume: 9 Issue: 1
Author(s): Markus Geissen, Harriet Mella, Armin Saalmuller, Martin Eiden, Juliane Proft, Eberhard Pfaff, Hermann M. Schatzl and Martin H. Groschup
Affiliation:
Keywords: PrP mutants, PrP conversion, Glycosylation and cellular trafficking, PrP seed formation
Abstract: Until now it is still not clear which structural elements of the prion protein (PrP) are involved in its conversion process. Characterisation of these essential regions would help to understand the conversion process itself and might help to develop specific therapeutic approaches to inhibit PrPres formation by dominant inhibitory mutations. To address this important question 33 evenly spaced insertion mutants were generated spanning the entire sequence of the murine 3F4- tagged PrP. The mutants were expressed by retroviral transduction in three different scrapie infected cell lines (ScN2a; SMB[RC040]; SMB[22F]). The convertibility was affected not only by introducing the insertion in the putatively refolded region (aa100-170), but also in the C-terminus of PrP (up to aa214). Moreover, dominant inhibitory effects on conversion were observed for PrP-mutants at four distinguished regions (aa100-112; aa130-154; aa166-172, aa196-200). Computer based structural analysis revealed that these segments were organized in two structurally clearly separated regions supporting the idea that they could function as protein-protein interaction sites which are necessary during seed formation.
Export Options
About this article
Cite this article as:
Geissen Markus, Mella Harriet, Saalmuller Armin, Eiden Martin, Proft Juliane, Pfaff Eberhard, Schatzl M. Hermann and Groschup H. Martin, Inhibition of Prion Amplification by Expression of Dominant Inhibitory Mutants - A Systematic Insertion Mutagenesis Study, Infectious Disorders - Drug Targets 2009; 9 (1) . https://dx.doi.org/10.2174/1871526510909010040
DOI https://dx.doi.org/10.2174/1871526510909010040 |
Print ISSN 1871-5265 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3989 |
- 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
-
Neuroprotective Effects of Drug-Induced Therapeutic Hypothermia in Central Nervous System Diseases
Current Drug Targets Immunopathology of Brucella Infection
Recent Patents on Anti-Infective Drug Discovery HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP): Still an Obscure Disease
Central Nervous System Agents in Medicinal Chemistry Isoquinolines: Important Cores in Many Marketed and Clinical Drugs
Anti-Cancer Agents in Medicinal Chemistry Electroacupuncture Reduces Hemiplegia Following Acute Middle Cerebral Artery Infarction with Alteration of Serum NSE, S-100B and Endothelin
Current Neurovascular Research Manipulation of Dendritic Cells for Tumor Immunity
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Potential Therapeutic Strategies of Phytochemicals in Neurodegenerative Disorders
Current Topics in Medicinal Chemistry Acute Symptomatic Seizures in Geriatric Patients with Multiple Risk Factors - A Diagnostic Challenge
Current Aging Science Possible Targets of Herbals for Type 3 Diabetes: A Review
Current Traditional Medicine Members of CRF Family and their Receptors: From Past to Future
Current Medicinal Chemistry Multidrug-Resistance (MDR) Proteins Develops Refractory Epilepsy Phenotype:Clinical and Experimental Evidences
Current Drug Therapy Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders
Current Molecular Medicine The Role of Viruses in Neurodegenerative and Neurobehavioral Diseases
CNS & Neurological Disorders - Drug Targets Immune Receptors, Cadherins and their Interactions
Current Immunology Reviews (Discontinued) Human ABC Transporters at blood-CNS Interfaces as Determinants of CNS Drug Penetration
Current Pharmaceutical Design New Antiviral Nucleoside Prodrugs Await Application
Current Medicinal Chemistry Nipah Virus: An Updated Review and Emerging Challenges
Infectious Disorders - Drug Targets Functions of S100 Proteins
Current Molecular Medicine The Current WHO Classification of Tumours of the Central Nervous System: Histopathology and Additional Diagnostic Methods
Current Medical Imaging Gene Therapy for Ischemic Brain Diseases
Current Gene Therapy