tailieunhanh - Báo cáo khoa hoc : Exchange of the HCC domain mediating double receptor recognition improves the pharmacodynamic properties of botulinum neurotoxin

The four-domain structure of botulinum neurotoxins (BoNTs) reflects their multistep intoxication process. The high toxicity of BoNTs primarily results from specific binding and uptake into neurons mediated by their 50-kDa cell-binding fragment (HC). X-ray crystallography data have revealed that the HCfragment consists of two domains of equal size, named the 25-kDa N-terminal half of HC(HCN) and the 25-kDa C-terminal half of HC(HCC). | IFEBS Journal Exchange of the HCC domain mediating double receptor recognition improves the pharmacodynamic properties of botulinum neurotoxin Andreas Rummel1 Stefan Mahrhold2 Hans Bigalke1 and Thomas Binz2 1 Institut fur Toxikologie Medizinische Hochschule Hannover Germany 2 Institut fur Biochemie Medizinische Hochschule Hannover Germany Keywords botulinum neurotoxin hybrid ganglioside-binding site HC fragment Hcc domain HCN domain Correspondence A. Rummel Institut fur Toxikologie Medizinische Hochschule Hannover D-30623 Hannover Germany Fax 49 5115328021 Tel 49 5115322819 E-mail These authors contributed equally to this work Received 25 March 2011 revised 20 May 2011 accepted 25 May 2011 doi The four-domain structure of botulinum neurotoxins BoNTs reflects their multistep intoxication process. The high toxicity of BoNTs primarily results from specific binding and uptake into neurons mediated by their 50-kDa cell-binding fragment HC . X-ray crystallography data have revealed that the HC fragment consists of two domains of equal size named the 25-kDa N-terminal half of HC HCN and the 25-kDa C-terminal half of HC HCC . In recent years the ganglioside-binding sites of all seven BoNT serotypes have been allocated to the HCC domain. For BoNT A BoNT B and BoNT G the protein receptor-binding site has been also been localized to the HCC domain. Here we demonstrate that the HCC serotype can modulate the affinity of the HC fragment for neuronal membranes as well as the potency of full-length BoNT by replacing the BoNT A HCC domain with the BoNT B HCC BoNT C HCC and BoNT E HCC domains which exhibit higher affinity for synaptosomes. Indeed the hybrids HCAB and HCAC display a higher affinity than wild-type HCA. Furthermore the potency of a BoNT A-based full-length hybrid containing the HCCB domain AAAB letters represent the serotype origin of the four domains was quadrupled as compared with wild-type BoNT A. .

• Báo cáo khoa học
• Scientific reports
• medical analysis
• environmental medicine
• neurotoxin
• molecular Biology
• genetics
• Biological information
• Lecture Genetics
• Human genetics
• Organelle genetics
• Bacterial genomes
• Non Mendelian inheritance
• Somatic mutation
• Genetics of cancer
• Cell division
• Model organisms
• Developmental genetics
• BRS Genetics
• Chromosomal morphology methods
• Cytogenetic disorders
• Genetics of metabolism
• Genetics of hemoglobinopathies
• Genetics of bleeding disorders
• Quantitative genetics
• Population genetics
• Evolutionary genetics
• Cancer genetics
• The genetic code
• Ebook Principles of Genetics
• Principles of Genetics
• Principles of Genetics (Sixth edition)
• The science of genetics
• Cellular reproduction
• Testing genetic hypotheses
• The techniques of molecular genetics
• Transposable genetic elements
• Inheritance of complex traits
• Applications of molecular genetics
• Genetics in medicine
• Birth defects
• Cancer genetics and genomics
• Risk assessment
• Genetic counseling
• Prenatal diagnosis and screening
• Personalized health care
• USMLE road map Genetics
• Mitochondrial dysfunction
• Congenital changes
• Genetics and cancer
• Genetics and common diseases
• Elseviers integrated review genetics
• Integrated review genetics
• Musculoskeletal disorders
• Neurologic diseases
• Cardiopulmonary disorders
• Modern molecular medicine
• Modern genetic techniques
• Molecular interactions
• Modular construction
• Extensions of mendelism
• The chromosomal basis of mendelism
• Variation in chromosome number
• The genetics of bacteria
• Summary of Doctoral Thesis
• Aquatic Products Processing
• Molecular genetics
• Shrimp breeding by growth trait
• Genetic variation
• Basic mechanisms
• Chromosomes in the cell
• Mechanisms of inheritance
• Hematologic genetics
• punicus Puzzle
• hydrophila
• Polymorphism
• Genomic Era
• Chronic Myelogenous Leukemia
• Colorectal Cancer
• Neurodegenerative Diseases
• Teratogenesi
• Medical Genetics
• Diagnostic Techniques
• Basic Genetics
• Mendels principles
• Mendels principles of heredity
• Mendels laws
• Single gene inheritance
• Chromosome theory
• Carriers of genes
• Gene linkage
• Mapping of genes
• DNA structure
• DNA replication
• DNA recombination
• Dissection through mutation
• Genetic analysis
• Gene structure
• Gene expression
• Protein synthesis
• Genetic code
• Digital analysis of DNA
• DNA fragmentation
• Restriction enzymes