Christopher Marang

All Publications

• The order of things: phosphate release or the power stroke, which does actomyosin do first? Frontiers in physiology Debold, E. P., Marang, C. P., Scott, B. D. 2025; 16: 1692606

  Abstract

  Myosins are a highly conserved super family of motor proteins that are responsible for driving a host of intracellular processes in eukaryotes, from muscle contraction to vesicular transport. Myosins can perform these tasks because they transduce chemical energy, from the hydrolysis of ATP into mechanical work, in the form of a power stroke. The key event in the transduction process is the putative coupling of Pi release with the power stroke; however, the timing and mechanism of coupling of these events remain unclear. Atomic structures of myosin, captured in intermediate states of its cross-bridge cycle, suggest that Pi release is required for the power stroke to occur and therefore must precede the power stroke. In contrast, most functional assays, which can measure myosin's structural dynamics with sub-millisecond temporal and nanometer spatial resolution, suggest that the power stroke occurs less than 1 ms after forming a strong bond with actin, while Pi release occurs 10-200 ms after binding to actin, suggesting that the power stroke precedes Pi release. A host of new studies and a few new models have been put forth in recent years to attempt to reconcile these seemingly conflicting findings. Although there is not yet a consensus on the order of these events, the new information provided by these efforts is transforming our understanding of how myosin transduces energy. This knowledge has important implications for elucidating the molecular basis of a myriad of myosin-associated diseases and, therefore, for the development of compounds to treat these diseases.

  View details for DOI 10.3389/fphys.2025.1692606

  View details for PubMedID 41384244

  View details for PubMedCentralID PMC12689349

• Characterizing the concentration and load dependence of phosphate binding to rabbit fast skeletal actomyosin. Proceedings of the National Academy of Sciences of the United States of America Marang, C. P., Petersen, D. J., Scott, B. D., Walcott, S., Debold, E. P. 2025; 122 (20): e2504758122

  Abstract

  Intensely contracting fast skeletal muscle rapidly loses the ability to generate force, due in part to the accumulation of phosphate (Pi) inhibiting myosin's force-generating capacity, in a process that is strain dependent. Crucial aspects of the mechanism underlying this inhibition remain unclear. Therefore, we directly determined the effects of increasing [Pi] on rabbit psoas muscle myosin's ability to generate force against progressively higher resistive loads in a laser trap assay, with the requisite spatial and temporal resolution to discern the mechanism of inhibition. Myosin's force-generating capacity decreased with increasing [Pi], an effect that became more pronounced at higher resistive loads. The decrease in force resulted from myosin's accelerated detachment from actin, which also increased at higher resistive forces. These data are well fit by a cross-bridge model in which Pi rebinds to actomyosin in a postpowerstroke, ADP-bound state before accelerating myosin's detachment from actin. Thus, these findings provide important molecular insight into the mechanism underlying the Pi-induced loss of force during muscle fatigue from intense contractile activity.

  View details for DOI 10.1073/pnas.2504758122

  View details for PubMedID 40359046

  View details for PubMedCentralID PMC12107134

• Force-dependence reveals phosphate's effect on the cross-bridge cycle, favoring a branched-pathway over a powerstroke-reversal Petersen, D. J., Marang, C., Scott, B., Debold, E. P., Walcott, S. CELL PRESS. 2025

  View details for Web of Science ID 001466121800265