Figure 2.
The four-pathway network for cardiac myosin unitary steps. An unloaded myosin powerstroke generally has two sequential enzymatic steps with Pi release driving the larger lever arm swing (nominal 5 nm step-size) followed by the ELC N-terminus binding actin and ADP release driving the smaller lever arm swing (3 nm step-size). The blue pathway has an 8 nm step-size where large and small steps are tightly coupled for the maximum lever arm swing. The green pathway is predominant with the 5 nm step accompanying product release. Occasionally Pi release with the 5 nm step is not immediately followed by ADP release because of lever arm strain inhibition at the lower thunderbolt allowing time for the subsequent ELC N-terminus binding and 3 nm step in the yellow pathway. Flux through the network pathways is variously distorted by loading. The red pathway denotes a solo-3+ nm step-size where myosin partially slips to releases Pi with approximately 1 nm net forward movement but then the ELC N-terminus binds actin permitting ADP release and completion of a 3 nm step. Myosin in the red pathway is observed here as a new 4 nm step-size occurring only in a high-force regime defined in the text. The ELC-ratchet strain inhibiting filter at the upper thunderbolt regulates the 3 nm part of the 5 + 3 nm pathway as well as the solo-3+ and 8 nm pathways (yellow, red and blue). ELC ratchet strain inhibits ATP binding and ELC N-terminus detachment from actin maintaining tension at peak isometric force. The lever arm strain inhibition at the lower thunderbolt regulates the 5 nm pathway (green) with strain inhibition of ADP release. The upper and lower thunderbolts are competing strain regulated checkpoints that modulate step-frequencies for quickly responding to changing force–velocity demands. Myosin flux through the network is denoted in the figure with fi for i = 1, 3, 4, 5 and 7, and identically to earlier work [25]. Flux calculations were not attempted here because the constraints limiting the flux values are sometimes qualitative as described in the text.