Mechanism(s) of regulation of the cardiac thin filament: new perspectives for a longstanding enigma

Abstract

Every heartbeat relies on cyclical interactions between my­osin thick and actin thin filaments orchestrated by rising and falling Ca2+ levels. The structural mechanism of the thin filament regulation by Ca2+ was mostly unknown until sin­gle particle approach to reconstruction of frozen hydrated thin filaments was developed. We resolved the structure of the native cardiac thin filament at physiological (systolic) Ca2+ levels to show that the two strands of the thin filament consist of a mixture of regulatory units, which are comprised of Ca2+-free, Ca2+-bound, or mixed (e.g.