Ronald A. Milligan, Ph.D.

Research

Work in my laboratory currently focuses on members of the myosin and kinesin superfamilies of motors. Our approach is to use cryo-EM and image analysis to calculate three-dimensional (3D) maps of the track-motor complexes at various stages in their movement cycles. The raw 3D maps provide the macromolecular envelopes of the complexes. Individual parts of the complexes such as discrete domains or light chains, are located within the envelopes by difference mapping. For example, a 3D map of myosin lacking a light chain is subtracted from an equivalent “wild type” map. The light chain is visualized as a density peak in the resulting difference map. In a similar fashion, specific amino acid residues are located in the molecular components by gold-cluster labeling and difference mapping. These three types of data - the macromolecular envelopes, the 3D locations of the component parts and the 3D locations of specific amino acid residues - enable us to build near-atomic models of the complexes from the x-ray crystal structures of the individual molecules.