A conformation spectrum analysis of the morphological states of myosin S1 in the presence of effectors

Abstract

The subfragment-1 (S1) of the contractile protein myosin is the postulated site of energy transduction in muscle. It is currently considered that a large conformational change in this moeity, which forms ‘cross-bridges’ between the thick (myosin based) and thin (actin based) filaments, is the mechanical driving force which leads to mutual sliding of the two types of filaments, and hence to contraction.

We have studied the possibility that S1 from skeletal myosin can in free solution (and in the absence of actin) be induced to undergo related changes in conformation, in the presence of a range of effectors whose action mimics stages of the contractile cycle. Analysis of the g(s ^*) profiles of S1 under these conditions, displayed after force-fitting of the known monomer mass as conformation spectra (CON-SPECs-[7]), shows that changes of the type associated with the contractile cycle are readily detected. There is full qualitative and extensive quantitative agreement between the magnitude of the changes seen and those predicted on the basis of hydrodynamic bead modeling and high resolution electron microscopy. Results from recently published X-ray crystallography of smooth muscle S1 [8] are also in general agreement with our findings.