Myosin dynamics during relaxation in mouse soleus muscle and modulation by 2'-deoxy-ATP.

This study of the dATP induced changes in myosin may be instructive for determining the structural changes desired for other potential myosin targeted molecular compounds to treat muscle diseases.
ABSTRACT: Here we used time-resolved small angle X-ray diffraction coupled with force measurements to study the structural changes in FVB mouse skeletal muscle sarcomeres during relaxation after tetanus contraction. To estimate the rate of myosin deactivation we followed the rate of the intensity recovery of the first-order myosin layer line (MLL1) and the restoration of the resting spacing of the third and sixth order of meridional reflection (SM3 and SM6 ) following tetanic contraction. A transgenic mouse model with elevated skeletal muscle dATP was used to study how myosin activators may affect soleus muscle relaxation. X-ray diffraction evidence indicates that with elevated dATP, myosin heads were extended closer to actin in resting muscle. Following contraction, there is a slight but significant delay in the decay of force relative to WT muscle while the return of myosin heads to an ordered resting state was initially slower, then became more rapid than in WT muscle. Molecular dynamics simulations of post-powerstroke myosin suggest that dATP induces structural changes in myosin that increases the surface area of the actin binding regions, promoting myosin interaction with actin. With dATP, myosin heads may remain in an activated state near the thin filaments following r...

Source: The Journal of Physiology - August 19, 2020 Category: Physiology Authors: Ma W, Childers M, Murray J, Moussavi-Harami F, Gong H, Weiss R, Daggett V, Irving T, Regnier M Tags: J Physiol Source Type: research