Three-dimensional structure of myosin subfragment-1: a molecular motor

Abstract

Directed movement is a characteristic of many living organisms and occurs as a result of the transformation of chemical energy into mechanical energy. Myosin is one of three families of molecular motors that are responsible for cellular motility. The three-dimensional structure of the head portion of myosin, or subfragment-1, which contains both the actin and nucleotide binding sites, is described. This structure of a molecular motor was determined by single crystal x-ray diffraction. The data provide a structural framework for understanding the molecular basis of motility.

Mechanism of force generation by myosin heads in skeletal muscle

“…Each myosin filament was assumed to contain two arrays of myosin heads separated by a bare zone 27,28 of length B (,160 nm). Each array has 49 layers of heads with axial periodicity d. The axial mass projection of each layer of heads was calculated from crystallographic data, with the catalytic domain (CD, heavy chain residues 1-707) of the head in its nucleotide-free actin-bound conformation 5,6 , and the light chain domain (LCD, heavy chain residues 707-843 and both light chains) tilted axially around the CD/LCD junction 7,8,12 . During isometric contraction the 707-843 axis was assumed to be at 608 to the filament axis 12 .…”

“…These motions occur to the same extent in models with and without a working stroke, so the phase 1 analysis provides an independent calibration of the X-ray interference method. Each layer of heads was represented by an atomic model with the catalytic domain in its nucleotide-free conformation 5,6 and a variable bend between the catalytic and light chain domains 7,8 (see Methods). The changes in I HA /I LA , S LA and S HA calculated from this model (Fig.…”

Kinesin motors as molecular machines

“…(53) The movement might represent a lever arm-like angle change of the coiled-coil stalk/ neck of Ncd, similar to the large rotation of the coiled-coil rod believed to occur in myosin. (55)(56)(57) A second displacement has been detected just before release of Ncd from the microtubule and has been postulated to be the large conformational change predicted to occur when ATP binds to the motor. (54) The structural basis of this movement has not yet been determined, although it may correspond to the rotation coupled to a translation of the relay helix, a4, detected in the kinesin motor KIF1A, which is thought to be triggered by binding of ATP to the motor.…”

Myosin cleft movement and its coupling to actomyosin dissociation

“…2 However, while crystal structures of myosin motor domains have been obtained for a number of nucleotide-bound states, the nature of the actin binding interaction has not been observed directly to date 2,3,8,10,11 . Residues involved in actin binding were identified by fitting the envelope of the myosin crystal structure into the electron micrograph density of decorated actin filaments.…”