Interacting-heads motif explains the X-ray diffraction pattern of relaxed vertebrate skeletal muscle
Division of Cell Biology and Imaging, Department of Radiology; Craig Lab
Bioimaging and Biomedical Optics | Biophysics | Cell Biology | Radiology
Electron microscopy (EM) shows that myosin heads in thick filaments isolated from striated muscles interact with each other and with the myosin tail under relaxing conditions. This "interacting-heads motif" (IHM) is highly conserved across the animal kingdom and is thought to be the basis of the super-relaxed state. However, a recent X-ray modeling study concludes, contrary to expectation, that the IHM is not present in relaxed intact muscle. We propose that this conclusion results from modeling with a thick filament 3D reconstruction in which the myosin heads have radially collapsed onto the thick filament backbone, not from absence of the IHM. Such radial collapse, by about 3-4 nm, is well established in EM studies of negatively stained myosin filaments, on which the reconstruction was based. We have tested this idea by carrying out similar X-ray modeling and determining the effect of the radial position of the heads on the goodness of fit to the X-ray pattern. We find that, when the IHM is modeled into a thick filament at a radius 3-4 nm greater than that modeled in the recent study, there is good agreement with the X-ray pattern. When the original (collapsed) radial position is used, the fit is poor, in agreement with that study. We show that modeling of the low-angle region of the X-ray pattern is relatively insensitive to the conformation of the myosin heads but very sensitive to their radial distance from the filament axis. We conclude that the IHM is sufficient to explain the X-ray diffraction pattern of intact muscle when placed at the appropriate radius.
DOI of Published Version
Koubassova NA, Tsaturyan AK, Bershitsky SY, Ferenczi MA, Padrón R, Craig R. Interacting-heads motif explains the X-ray diffraction pattern of relaxed vertebrate skeletal muscle. Biophys J. 2022 Apr 19;121(8):1354-1366. doi: 10.1016/j.bpj.2022.03.023. Epub 2022 Mar 19. PMID: 35318005. Link to article on publisher's site
Koubassova NA, Tsaturyan AK, Bershitsky SY, Ferenczi MA, Padron R, Craig RW. (2022). Interacting-heads motif explains the X-ray diffraction pattern of relaxed vertebrate skeletal muscle. Radiology Publications. https://doi.org/10.1016/j.bpj.2022.03.023. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/678