Blebbistatin stabilizes the helical order of myosin filaments by promoting the switch 2 closed state
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2008-07-05Keywords
ActinsAdenosine Diphosphate
Animals
Apyrase
Arachnida
Heterocyclic Compounds with 4 or More Rings
Muscles
Myosins
Phosphates
Protein Binding
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Blebbistatin is a small-molecule, high-affinity, noncompetitive inhibitor of myosin II. We have used negative staining electron microscopy to study the effects of blebbistatin on the organization of the myosin heads on muscle thick filaments. Loss of ADP and Pi from the heads causes thick filaments to lose their helical ordering. In the presence of 100 microM blebbistatin, disordering was at least 10 times slower. In the M.ADP state, myosin heads are also disordered. When blebbistatin was added to M.ADP thick filaments, helical ordering was restored. However, blebbistatin did not improve the order of thick filaments lacking bound nucleotide. Addition of calcium to relaxed muscle homogenates induced thick-thin filament interaction and filament sliding. In the presence of blebbistatin, filament interaction was inhibited. These structural observations support the conclusion, based on biochemical studies, that blebbistatin inhibits myosin ATPase and actin interaction by stabilizing the closed switch 2 structure of the myosin head. These properties make blebbistatin a useful tool in structural and functional studies of cell motility and muscle contraction.Source
Biophys J. 2008 Oct;95(7):3322-9. Epub 2008 Jul 3. Link to article on publisher's site
DOI
10.1529/biophysj.108.137067Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39270PubMed ID
18599626Related Resources
ae974a485f413a2113503eed53cd6c53
10.1529/biophysj.108.137067