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 a ssembly of thick filaments in vertebrate striated muscle. To investiga te the correlation of titin domain patterns with the architecture of t he thick filament at its end, we have investigated the axial position of titin epitopes at the thick-filament/I-band junction. Antibodies ag ainst immunoglobin (Ig) domains N and C-terminal to the unique block o f six fibronectin-3 (fn3) domains in this region were used. The distan ce between these epitopes confirms the idea that titin is laid out lin early along the thick filament with each domain measuring about 1 nm i n length. Our data demonstrate that the gap of myosin crossbridges nea r 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 r eflects the arrangement of the myosin heads, at least at the end of th e A-band. It seems likely that an alteration in the interaction betwee n myosin and the titin fn3 domains towards the end of the thick filame nt is important for the formation of the crossbridge gap and thus the termination of the thick filament. (C) 1996 Academic Press Limited