Plectin repeats and modules: strategic cysteines and their presumed impact on cytolinker functions.
Plectin, a member of the cytolinkers protein family, plays a crucial role in cells as a stabilizing element of cells against mechanical stress. Its absence results in muscular dystrophy, skin blistering, and signs of neuropathy. The C-terminal domain of plectin contains several highly homologous repeat domains that also occur in other cytolinkers. Secondary structure analysis revealed that the building block of these domains, the PLEC repeat, is similar to the ankyrin repeat. We present a model that attempts to explain how the C-terminal domain, which comprises approximately 1900 amino acid, could be stabilized to maintain its structural integrity even under extensive mechanical stress. In this model, larger solenoid modules formed from PLEC repeats can be disulfide-bridged via conserved cysteines. Our hypothesis suggests that this process could be mediated by cytoplasmic NOS-generated products, such as the radical peroxynitrite. Reinforcement of molecular structure would provide a rationale why during exercising or physical stress radicals are formed without necessarily being deleterious. This article contains supplementary material that may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/23/v23_11.1064.html.
Janda
L
L
Institute of Biochemistry and Molecular Cell Biology, University of Vienna, Austria.
Damborský
J
J
Rezniczek
G A
GA
Wiche
G
G
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000737:chemistry* / Q000502:physiology; D003545:Cysteine / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry* / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016877:Oxidants / Q000502:physiology; D051190:Plectin; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid / Q000502:physiology*
D017487:Ankyrins; D007381:Intermediate Filament Proteins; D016877:Oxidants; C495332:PLEC protein, human; D051190:Plectin; D003545:Cysteine