Molecular mechanisms of the regulation of ATPase cycle in striated muscle

Charles Redwood,Olga Karpicheva,Yuri Borovikov

doi:10.1038/npre.2007.1391.1

Abstract

AbstractNew data on the molecular mechanism of the regulation of ATPase cycle by troponin-tropomyosin system have been obtained in reconstructed muscle fibers by using the polarized fluorescence technique, which allowed us following the azimuthal movements of tropomyosin, actin subdomain-1 and myosin SH1 helix motor domain during the sequential steps of ATPase cycle. We found that tropomyosin strands "rolling" on thin filament surface from periphery to center at ATPase cycle increases the amplitudes of multistep changes in special arrangement of SH1 helix and subdomain-1 at force generation states. These changes seem to convey to actin monomers and to myosin "lever arm", resulting in enhance of the effectiveness of each cross-bridge work. At high-Ca^2+^ troponin, a shift of tropomyosin strands further to center at strong-binding states increases this effect. At low-Ca^2+^ troponin "freezes" tropomyosin and actin in states typical for weak-binding states, resulting in disturbing the teamwork of actin and myosin.

Highlights

New data on the molecular mechanism of the regulation of ATPase cycle by troponintropomyosin system have been obtained in reconstructed muscle fibers by using the polarized fluorescence technique, which allowed us following the azimuthal movements of tropomyosin, actin subdomain-1 and myosin SH1 helix motor domain during the sequential steps of ATPase cycle
We found that tropomyosin strands “rolling” on thin filament surface from periphery to center at ATPase cycle increases the amplitudes of multistep changes in special arrangement of SH1 helix and subdomain-1 at force generation states
Polarized fluorimetry is a highly sensitive method for studying conformational changes of contractile proteins in muscle fibers[9,10]. Using this method, has shown previously that the formation of strong-binding of myosin to actin in the muscle fiber induces the change in a tilt angle of myosin motor domain[11,12,13,14], in a rotation of myosin “lever arm”[15,16], and in a shift of subdomain-1 and subdomain-2 of actin[17]

Summary

Introduction

New data on the molecular mechanism of the regulation of ATPase cycle by troponintropomyosin system have been obtained in reconstructed muscle fibers by using the polarized fluorescence technique, which allowed us following the azimuthal movements of tropomyosin, actin subdomain-1 and myosin SH1 helix motor domain during the sequential steps of ATPase cycle. We found that tropomyosin strands “rolling” on thin filament surface from periphery to center at ATPase cycle increases the amplitudes of multistep changes in special arrangement of SH1 helix and subdomain-1 at force generation states. These changes seem to convey to actin monomers and to myosin “lever arm”, resulting in enhance of the effectiveness of each cross-bridge work. The isomerization of myosin heads to a strong complex with F-actin shifts TM further to the periphery of thin filaments, to "open" state[8] While these tropomyosin movements are well established, the molecular mechanism of regulation of actin-myosin interaction by troponintropomyosin complex during ATPase cycle is an open and intriguing question. Since the modification of the cystein residues does not affect the functional properties of these proteins[13,22,23], it is possible to suggest that the movements of SH1 helix, actin subdomain-1 and TM strands on thin filament surface take place during the ATPase cycle in native muscle fiber

Objectives

Findings

Methods