Interacting-Heads Motif Explains the X-Ray Diffraction Pattern of Relaxed Vertebrate Skeletal Muscle

Koubassova, N.A.; Tsaturyan, A.K.; Bershitsky, S.Y.; Ferenczi, M.A.; Padrón, R.; Craig, R.

Авторы: Koubassova Natalia A., Tsaturyan Andrey K., Bershitsky Sergey Y., Ferenczi Michael A., Padrón Raúl, Craig Roger
Журнал: Biophysical Journal
Год издания: 2022
Издательство: Biophysical Society
Местоположение издательства: United States
DOI: 10.1016/j.bpj.2022.03.023
Аннотация: Electron microscopy shows that myosin heads in thick filaments isolated from striatedmuscles 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 tobe 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 thatthis conclusion results from modeling with a thick filament 3D reconstruction in which the myosinheads 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 stainedmyosin filaments, on which the reconstruction was based. We have tested this idea by carryingout similar X-ray modeling and determining the effect of the radial position of the heads on thegoodness of fit to the X-ray pattern. We find that when the IHM is modeled into a thick filamentat a radius 3-4 nm greater than that modeled in the recent study, there is good agreement withthe X-ray pattern. When the original (collapsed) radial position is used, the fit is poor, inagreement with that study. We show that modeling of the low-angle region of the X-ray patternis relatively insensitive to the conformation of the myosin heads but very sensitive to their radialdistance 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.
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Interacting-Heads Motif Explains the X-Ray Diffraction Pattern of Relaxed Vertebrate Skeletal Muscleстатья

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