ABSTRACT
The molecular motor myosin II consists of two myosin heavy chains (MyHC), two regulatory (RLC), and two essential (ELC) myosin light chains. In particular, crystal structures, functional analysis of single myosin molecules, and genetically engineered animal models with mutated myosin subunits shed new light on the functional roles of ELC. This review will concentrate on the physiological and pathophysiological impact of the ELC in vertebrate muscle types, i.e., skeletal muscle fibers, cardiomyocytes, and smooth muscle cells. First, structures, interaction interfaces, and phosphorylation of ELC will be considered. Second, functional roles of ELC interactions domains and ELC isoforms and, third, pathophysiological aspects of ELC will be discussed. Based
on its multiple protein-protein interaction interfaces, ELC is demonstrated here as a multitasking protein factor, modulating a variety of myosin motor and, hence muscle contraction features. These comprise the following: (i) ELC/MyHC interaction, which regulates stiffness, unitary force development, working stroke, duty cycle, and in vitro sliding velocity of actin filaments of myosin molecules but not actin-activated myosin ATPase activity. Furthermore, ELC/MyHC interaction could be associated with the regulation of interfilament space of the sarcomeres and elementary steps of the cross-bridge cycle, association constant of ATP binding and equilibrium constant of the cross-bridge detachment step, Ca2+ sensitivity of force generation, power output, relaxation of the heart, and the stretch activation response. Perturbation of ELC/MyHC interaction interfaces by a variety of missense mutations associates with familial hypertrophic cardiomyopathy, further documenting the important functional roles of ELC. (ii) ELC/actin interaction slows down maximal shortening velocity, cross-bridge detachment rate, and in vitro sliding velocity of actin filaments and increases fiber stiffness (rigor), but does not affect isometric force generation.
