Titin domain patterns correlate with the axial disposition of myosin at the end of the thick filament.
Titin has been suggested to act as a molecular ruler for the precise assembly of thick filaments in vertebrate striated muscle. To investigate the correlation of titin domain patterns with the architecture of the thick filament at its end, we have investigated the axial position of titin epitopes at the thick-filament/I-band junction. Antibodies against immunoglobin (Ig) domains N and C-terminal to the unique block of six fibronectin-3 (fn3) domains in this region were used. The distance between these epitopes confirms the idea that titin is laid out linearly along the thick filament with each domain measuring about 4 nm in length. Our data demonstrate that the gap of myosin crossbridges near the end of the thick filament closely correlates with the stretch of six fn3 domains, and that the last two crossbridges are at the level of the first two groups of fn3 domains which were previously assigned to the I-band. We conclude that the pattern of groups of fn3 domains reflects the arrangement of the myosin heads, at least at the end of the A-band. It seems likely that an alteration in the interaction between myosin and the titin fn3 domains towards the end of the thick filament is important for the formation of the crossbridge gap and thus the termination of the thick filament.
Bennett
P M
PM
Randall Institute, King's College London, UK.
Gautel
M
M
D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D064211:Connectin; D018604:Epitope Mapping; D005353:Fibronectins / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology* / Q000648:ultrastructure; D009210:Myofibrils / Q000502:physiology / Q000648:ultrastructure; D009218:Myosins / Q000502:physiology*; D010215:Papio; D011494:Protein Kinases / Q000502:physiology*; D016658:Psoas Muscles; D011817:Rabbits; D012518:Sarcomeres / Q000502:physiology / Q000648:ultrastructure
D064211:Connectin; D005353:Fibronectins; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases; D009218:Myosins