The biology of desmin filaments: how do mutations affect their structure, assembly, and organisation?
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.
Department of Cell Biology, German Cancer Research Center (DKFZ), Heidelberg D-69120, Germany.
Harald
H
Bär
Sergei V
SV
Strelkov
Gunnar
G
Sjöberg
Ueli
U
Aebi
Harald
H
Herrmann
D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D003893:Desmin / Q000737:chemistry*; D019281:Dimerization; D006801:Humans; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000648:ultrastructure; D009135:Muscular Diseases / Q000473:pathology*; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012518:Sarcomeres; D017386:Sequence Homology, Amino Acid; D014746:Vimentin / Q000737:chemistry
D003893:Desmin; D014746:Vimentin