Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function

Alamo, L.; Koubassova, N.; Pinto, A.; Gillilan, R.; Tsaturyan, A.; Padrón, R.

Авторы: Lorenzo Alamo, Natalia Koubassova, Antonio Pinto, Richard Gillilan, Andrey Tsaturyan, Raúl Padrón
Журнал: Biophysical Reviews
Том: 9
Номер: 9
Год издания: 2017
Издательство: Springer Verlag
Местоположение издательства: Germany
Первая страница: 461
Последняя страница: 480
DOI: 10.1007/s12551-017-0295-1
Аннотация: The tarantula skeletal muscle X-ray diffraction pattern suggested that the myosin heads were helically arranged on the thick filaments. Electron microscopy (EM) of negatively stained relaxed tarantula thick filaments revealed four helices of heads allowing a helical 3D reconstruction. Due to its low resolution (5.0 nm), the unambiguous interpretation of densities of both heads was not possible. A resolution increase up to 2.5 nm, achieved by cryo- EM of frozen-hydrated relaxed thick filaments and an iterative helical real space reconstruction, allowed the resolving of both heads. The two heads, “free” and “blocked”, formed an asymmetric structure named the “interacting- heads motif” (IHM) which explained relaxation by self-inhibition of both heads ATPases. This finding made tarantula an exemplar system for thick filament structure and function studies. Heads were shown to be released and disordered by Ca -activation through myosin regulatory light chain phosphorylation, leading to EM, small angle X-ray diffraction and scattering, and spectroscopic and biochemical studies of the IHM structure and function. The results from these studies have consequent implications for understanding and explaining myosin super-relaxed state and thick filament activation and regulation. A cooperative phosphorylation mechanism for activation in tarantula skeletal muscle, involving swaying constitutively Ser35 monophosphorylated free heads, explains super-relaxation, force potentiation and post-tetanic potentiation through Ser45 mono-phosphorylated blocked heads. Based on this mechanism, we propose a swaying-swinging, tilting crossbridge-sliding filament for tarantula muscle contraction.
Добавил в систему: Цатурян Андрей Кимович

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Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and functionстатья

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