The proteolytic susceptibilities of specific sites in the LC1 and LC2 N-termini were modulated by ionic strength in myosin (a species able to form filaments) but not in S1. (a) In the presence of Ca'+ or Mg", the proteolytic susceptibility (apparent initial reaction rate) showed a sharp discontinuity at a critical ionic concentration similar for LCl', LC2 ' and LC2" cleavages. (b) The susceptibility of LC1' and LC2" was higher at low ionic concentration in the more compact structure of the filament than in the dissociated form at high ionic concentration. (c) The ionic concentration effect was no longer observed with species unable to form filaments. (d) This effect occurred at a critical ionic concentration markedly different from the critical concentration at which the monomer-filament equilibrium was found.These observations lead to the following conclusions. (a) The ionic concentration effect is an attribute of the filament structure. (b) In the filament the faster cleavage at sites (LC1' and LC2") near the LC1 and LC2 N-termini are due to an extended configuration of the N-terminal segment binding to a site in the filament structure. (c) The slower rate of formation of LC2' in the filament indicates that the N-terminal segment of LC2 binds more tightly to the structure than that of LC1. (d) The critical ionic concentration is not that of the filament -monomer equilibrium but corresponds to the order-disorder transition of the heads in the filament. These results suggest that the N-termini of the light chains (here in striated muscles) play a role in a secondary regulatory mechanism. The analysis of these regions may contribute to our understanding of the altered activity and regulation seen in such diseases as idiopathic dilated cardiomyopathy [Margossian, S. S., White, H. D., Caulfield, J. B., Norton, P., Taylor, s. & Slayter, H. s. (1992) Circulation 85, 2720-17331.The central event in muscle contraction is the interaction of actin and myosin in the presence of Mg-ATP. Since the part of myosin which interacts with actin is the head, the complex of actin and S1 is currently considered as a model system of the interaction between actin and myosin. There have been several attempts to solve the structure of this complex [ l , 21. The choice of this model was further supported by the observation that, on S1-coated surfaces, S1 appears to be a sufficient structure to sustain the movement of actin filaments [3], suggesting that the stroke results essentially from a transconformation of the myosin head (review in [4]).However Toyoshima et al. [3] have reported that the sliding velocity was highest with heavy meromyosin (HMM; 6-8 p d s , 30°C) and is only 33-25% of this value with S1. Thus the higher integrated structure found in HMM may be suspected of imparting a better efficiency to the system where a contribution of the S2 hinge segment could be suggested. In myosin thick filament, a more highly integrated system, physiological effectors were observed to govern the position of the heads close to or out fro...