Biochemistry of Mechanoenzymes: Biological Motors for Nanotechnology

Abstract

Nanotechnology produces and exploits moieties whose valuable properties are attributable to their precise structure sub-micron architectures, and promises to be among the most important emerging scientific areas of the 21st century (Feynman, 1959; Lee, 1998a,b). The dearth of wholly synthetic, functional nanocomponents is a major technological impediment to this endeavor at present (Lowe, 2000). This lack is particularly critical for complex functionalities such as molecular motors, sensing devices and other applications requiring the ordered interaction of multiple nanocomponents (Lee et al., in press-a, press-b). Nature has evolved a selection of (nanoscale) mechanoenzymes that transduce chemical energy into mechanical energy in living creatures. While it is possible to create limited synthetic nanomotors (Lowe, 2000), it is also feasible to build hybrid (synthetic-biological) nanodevices that contain mechanoenzymes. Synthetic nanomaterials can be used to organize functional biological macromolecules such that the construct can perform useful work. Such devices are called nanobiological or nanobiotechnological devices (Jelinski, 1999; Lee, 1998a,b; Lee et al., in press-a, press-b), and the general strategy is becoming an orthodox approach to the construction of functional nanostructures, particularly for therapeutic nanodevices. A number of nanobiological devices incorporating mechanoenzymes have been constructed in the course of characterization of biological motors (Ishijima and Yanagida, 2001; Mehta et al., 1999a,b; Vale et al., 1996; Vale and Toyoshima, 1988; Walker et al., 2000; Yang et al., 1990). For instance, microtubules (and other filamentous protein structures, see below) have been immobilized to substrates in cell-free systems and used as tracks to guide the transport of membrane vesicles or synthetic cargos by motor proteins that are cognates of the protein filaments. Conversely, motor proteins have been attached to substrates and used to transport “shuttles” composed of fragments of the cognate protein filaments (Dennis et al., 1999). Proteins often exhibit multileveled modularity, in which particular functions of polypeptides are often delimited to particular domains of a protein or to particular proteins of a multiprotein complex. It is often possible to isolate desired functions as small domains of proteins or multiprotein subassemblies from larger supramolecular complexes, and assemble those isolated functional domains into a nanobiological device. This strategy is as applicable to mechanoenzymes as it is to other biological structures, and several have been isolated from their native contexts and assembled into functional nanobiological devices (Dennis et al., 1999; Hess et al., 2002; Noji et al., 1997; Soong et al., 2000; Spudich et al., 1985; Vale et al., 1985; Yanagida et al., 1984). While we agree that exhaustive knowledge of mechanism is not required to build semi-biological nanodevices (Drexler, 1999), successful use of mechanoenzymes in nanodevices nonetheless requires sophisticated knowledge of their diversity and biochemical and physical properties. In this review we will discuss a selection of available mechanoenzymes, describe briefly how they function in biological systems, and provide a perspective on their strengths and limitations as prefabricated components of nanobiological devices.