title: Solution structure of heavy meromyosin by small-angle scattering.
abstract: Elucidation of x-ray crystal structures for the S1 subfragment of myosin afforded atomic resolution of the nucleotide and actin binding sites of the enzyme. The structures have led to more detailed hypotheses regarding the mechanisms by which force generation is coupled to ATP hydrolysis. However, the three-dimensional structure of double-headed myosin consisting of two S1 subfragments has not yet been solved. Therefore, to investigate the overall shape and relative orientations of the two heads of myosin, we performed small-angle x-ray and neutron scattering measurements of heavy meromyosin containing all three light chains (LC(1-3)) in solution. The resulting small-angle scattering intensity profiles were best fit by models of the heavy meromyosin head-tail junction in which the angular separation between heads was less than 180 degrees. The S1 heads of the best fit models are not related by an axis of symmetry, and one of the two S1 heads is bent back along the rod. These results provide new information on the structure of the head-tail junction of myosin and indicate that combining scattering measurements with high resolution structural modeling is a feasible approach for investigating myosin head-head interactions in solution.
authors.affiliation: Department of Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA. spharris@physiology.wisc.edu
authors.forename: Samantha P
authors.initials: SP
authors.lastname: Harris
authors.forename: William T
authors.initials: WT
authors.lastname: Heller
authors.forename: Marion L
authors.initials: ML
authors.lastname: Greaser
authors.forename: Richard L
authors.initials: RL
authors.lastname: Moss
authors.forename: Jill
authors.initials: J
authors.lastname: Trewhella
mesh_terms: D000818:Animals; D002499:Centrifugation, Density Gradient; D008958:Models, Molecular; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry; D018657:Muscle Fibers, Slow-Twitch; D018482:Muscle, Skeletal / Q000737:chemistry; D015879:Myosin Subfragments / Q000737:chemistry* / Q000302:isolation & purification; D009502:Neutrons; D011487:Protein Conformation; D011817:Rabbits; D012542:Scattering, Radiation
chemical_list: D015879:Myosin Subfragments