UNDERSTANDING THE DESIGN OF MOLECULAR MOTORS

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DESCRIPTION (Adapted from abstract): Directed movement is one of the defining characteristics of life. When we wonder if something is alive, we usually check to see if it is moving. Within a single cell we find an astounding collection of the most marvelous systems for producing motion. These biological motors are worthy of study not only for their intrinsic interest as masterpieces of "nanotechnology", but because their function is crucial for normal health. Important examples of microtubule-based motion include movement of chromosomes during cell division, the translocation of various intracellular membrane bound organelles, and the transport of materials from the cell body of neurons to their distant termini. Basic information about these motor systems has an unusually direct and immediate connection to human health. Agents that interfere with microtubule-based motile systems have therapeutic applications in humans: colchicine, used for in gouty arthritis; vincristine, vinblastine, and taxol, used for their anti-mitotic effects against a variety of neoplasms; griseofulvin, an anti-fungal agent; and others. Besides these medicinal uses, agents that affect the microtubule-based motile apparatus are significant for human health in equally important non-therapeutic ways, such as their widespread use as pesticides and fungicides. The goal of this research is to discover, in terms of 3D atomic structure, how proteins that act as microtubule-based molecular motors produce motion, and why different motors move in very different ways. The research focuses on two microtubule-based motors, kinesin and ncd, which move in opposite directions. The aim is to create, starting from these two motors, a library of new motors with different motile properties, then determine their structure, and thereby to elucidate the structural features that distinguish the biologically important characteristic classes of motile behavior.