Myosin ATP Turnover Rate: a Mechanism Involved in Thermogenesis in Resting Skeletal Muscle Fibers

Abstract

muscles subjected to 25 hz stimulation (flight frequency) are partially fused with (likely) little crossbridge turnover. To assess the structural correlates of temperature gradients, we performed small-angle x-ray fiber diffraction measurements as a function of position along the dorsal-ventral thermal gradient in intact moth thoraces. The equatorial intensity ratio (I 20 /I 10 ) in unstimulated muscle increased by~25% in the first 1 À1.5 mm traversing from dorsal to ventral, implying that increased temperature was associated with increased association of the myosin heads with the thin filaments presumably predisposing them towards more productive acto-myosin interaction. Interestingly, X-ray patterns from skinned muscle preparations improved with increasing temperature indicating better structural order. Together, these observations suggest that cooler, superficial muscles may act mainly as elastic energy storage, whereas warmer deeper muscles may do the bulk of the mechanical work.

Atomic model of the human cardiac muscle myosin filament

“…Moreover, X-ray diffraction studies of mouse heart muscle (34) have shown an increase in the proximity of the heads to actin and thus a displacement of the heads away from the backbone upon phosphorylation. Conversely, in the dephosphorylated state, the myosin heads would be predicted to be tilting back toward the backbone surface, as observed in our structure, and forming interactions, as proposed by Stewart and colleagues (31)(32)(33) for the SRX state.…”

“…The locations we identify for the myosin heads are quite close to the backbone, and the groupings of three crowns show well-defined interactions between myosin head pairs in adjacent crowns. A head conformation recently identified biochemically has been called the superrelaxed (SRX) state, in which the myosin ATPase activity is inhibited (31)(32)(33). It was concluded that the myosin heads in the SRX state are strongly stabilized on the backbone of the thick filament and have the J-like motif (11).…”

Myosin light chain phosphorylation enhances contraction of heart muscle via structural changes in both thick and thin filaments

“…Although many structural details of these interactions remain unclear, their effect is to stabilize a population of myosin heads, probably the majority of heads in the region of the filament containing MyBP-C, in a roughly helical lattice on the surface of the thick filaments (Fig. 1A), in which they are unavailable for binding to actin in the thin filaments or hydrolyzing ATP (41,42), features that define this as a functional OFF state. These interactions between filament components are lost in the ON state of the thick filament (Fig.…”

Myosin filament activation in the heart is tuned to the mechanical task

“…The textbook model for the activation of contraction indicates that the binding to actin of myosin motors from the neighboring thick filament is controlled by a calcium-dependent structural change in the thin filament. However, in these muscles at rest, most of the myosin motors are in the off state and packed into helical tracks with 43-nm periodicity on the surface of the thick filaments (1-4), making them unavailable for binding to the thin filament and ATP hydrolysis (5,6). Recent X-ray diffraction experiments on single fibers from skeletal muscle showed that, in addition to the canonical thin filament activation system, a thick filament mechanosensing mechanism provides a way for selective unlocking of myosin motors during high load contraction (7).…”