Author:

Keywords:

Amino Acid Sequence, Animals, Cell Nucleus, Cytoskeleton, Desmin, Dimerization, Humans, Microscopy, Electron, Microscopy, Fluorescence, Models, Biological, Models, Genetic, Models, Molecular, Molecular Sequence Data, Muscle Cells, Muscular Diseases, Mutation, Protein Structure, Secondary, Protein Structure, Tertiary, Sarcomeres, Sequence Homology, Amino Acid, Vimentin, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biophysics, Cell Biology, intermediate filaments, filament assembly, desminopathy, desmin-related myopathy, INTERMEDIATE-SIZED FILAMENTS, ALPHA-B-CRYSTALLIN, SKELETAL MYOPATHY, MYOFIBRILLAR MYOPATHY, SMOOTH-MUSCLE, DE-NOVO, IMMUNOCYTOCHEMICAL ANALYSIS, RESTRICTIVE CARDIOMYOPATHY, ATOMIC-STRUCTURE, VIMENTIN-FREE, 0601 Biochemistry and Cell Biology, 0608 Zoology, 3101 Biochemistry and cell biology

Abstract:

Desmin, the major intermediate filament (IF) protein of muscle, is evolutionarily highly conserved from shark to man. Recently, an increasing number of mutations of the desmin gene has been described to be associated with human diseases such as certain skeletal and cardiac myopathies. These diseases are histologically characterised by intracellular aggregates containing desmin and various associated proteins. Although there is progress regarding our knowledge on the cellular function of desmin within the cytoskeleton, the impact of each distinct mutation is currently not understood at all. In order to get insight into how such mutations affect filament assembly and their integration into the cytoskeleton we need to establish IF structure at atomic detail. Recent progress in determining the dimer structure of the desmin-related IF-protein vimentin allows us to assess how such mutations may affect desmin filament architecture.