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bioRxiv · 10.1101/2025.08.07.669198

Lever arm Flexibility Controls the extent of (Un)coupling to the Motor Domain in Myosin Motors

Mugnai, M. L.·Goldtzvik, Y.·Thirumalai, D.
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Abstract

Dimeric myosin motors, with both heads simultaneously bound to filamentous actin, are in a frustrated conformation. The lever arm of each head would prefer to orient forward, but the inter-head tension hinders the relaxation to the state favored by a myosin monomer. Here, we investigate theoretically the impact of lever arm stiffness and coupling to the head domain using a polymer model. The theory for MV and MVI qualitatively reproduce the salient experimental observations. Furthermore, we construct chimeras in which the lever arm and head domains are swapped, and predict that the fluctuations of the LH lever arm of MVI are strongly impacted by the stiffness of the lever arm. Finally, by continuously and independently varying the lever arm persistence length and the strength of its coupling to the head domain we predict their roles in altering the average geometry and conformational flexibility of the dimer. We explore conditions under which LH lever arm flexibility and angle with respect to F-actin lead to coupling to the motor domain. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/669198v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1c27772org.highwire.dtl.DTLVardef@3015a9org.highwire.dtl.DTLVardef@de48eaorg.highwire.dtl.DTLVardef@1853176_HPS_FORMAT_FIGEXP M_FIG For Table of Contents Use Only C_FIG

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Mugnai, M. L., Goldtzvik, Y., Thirumalai, D.. 2025-08-11. Lever arm Flexibility Controls the extent of (Un)coupling to the Motor Domain in Myosin Motors. https://doi.org/10.1101/2025.08.07.669198

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