Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and funct
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Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function Lorenzo Alamo 1 & Natalia Koubassova 2 & Antonio Pinto 1 & Richard Gillilan 3 & Andrey Tsaturyan 2 & Raúl Padrón 1
Received: 17 May 2017 / Accepted: 27 July 2017 # International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany 2017
Abstract 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, Bfree^ and Bblocked^, formed an asymmetric structure named the Binteracting-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 Ca2+-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 This article is part of a Special Issue on ‘Latin America’ edited by Pietro Ciancaglini and Rosangela Itri. * Raúl Padrón [email protected] 1
Centro de Biología Estructural BHumberto Fernández-Morán^, Instituto Venezolano de Investigaciones Científicas (IVIC), Apdo. 20632, Caracas 1020A, Venezuela
2
Institute of Mechanics, Moscow State University, Mitchurinsky prosp. 1, Moscow 119992, Russia
3
Macromolecular Diffraction Facility, Cornell High Energy Synchrotron Source, Ithaca, NY, USA
mechanism for activation in tarantula skeletal muscle, involving swaying constitutively Ser35 mono-phosphorylated free heads, explains super-relaxation, force potentiation and posttetanic potentiation through Ser45 mono-phosphorylated blocked heads. Based on this mechanism, we propose a swaying-swinging, tilting crossbridge-sliding filament for tarantula muscle contraction. Keywords Myosin filaments . Myosin heads . Muscle . Myosin interacting-heads motif . Tarantula
Introduction Our understanding of how muscle contraction occurs, the sliding filament model, is based on two pioneering works (Huxley and Niedergerke 1954; Huxley and Hanson 1954) showing that on contraction the sarcomere shortens by the sliding of two protein filament sets, the thin and thick filaments (see Hitchcock-DeGregori and Irving 2014). A need to understand this
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