STRUCTURE OF MOLECULAR TRACKS AND MOTORS. R.A. Milligan, Department of Cell Biology, The Scripps Research Institute' 10550 N. Torrey Pines Road, La Jolla, CA 92037 U.S.A

Molecular motors belonging to the myosin and kinesin superfamilies utilize ATP to move along their respective F-actin and microtubule tracks. The track-motor complexes have not been amenable to crystallization so x-ray crystallographic investigations have focused on structure determinations of the individual proteins. Although providing detailed descriptions of the structure of each protein, this approach cannot reveal the geometry of interaction of the proteins or the conformational changes which occur during the mechanochemical cycle. To obtain this information, we use electron microscopy and image analysis to calculate three dimensional maps of the track-motor complexes at moderate resolution (1.5-3.0nm). Recently, we have been investigating conformational changes in the motors in the response to nucleotide binding. In smooth muscle myosin (a collaboration with H.L. Sweeney, U. Penn.) and brush border myosin I, there are large changes in the orientation of the light-chaincontaining tail of the motor when MgADP binds to the actin-myosin complex. The light-chain region of the molecule seems to act as a rigid lever arm, pivoting about a point located near the sulphydrylcontaining region of the myosin motor domain. The reorientation of the light-chain regions that we have observed could account for a step of 3.5nm in smooth muscle myosin and <7nm in BBMD in response to ADP release. Similar experiments aimed at visualizing conformational changes in kinesin motors are in progress.