Molecular motors - a paradigm for mutant analysis

Molecular motors perform essential functions in the cell and have the poten tial to provide insights into the basis of many important processes. A uniq ue property of molecular motors is their ability to convert energy from ATP hydrolysis into work, enabling the motors to bind to and move along cytosk eletal filaments. The mechanism of energy conversion by molecular motors is not yet understood and may lead to the discovery of new biophysical princi ples, Mutant analysis could provide valuable information, but it is not obv ious how to obtain mutants that are informative for study. The analysis pre sented here points out several strategies for obtaining mutants by selectio n from molecular or genetic screens, or by rational design. Mutants that ar e expected to provide important information about the motor mechanism inclu de ATPase mutants, which interfere with the nucleotide hydrolysis cycle, an d uncoupling mutants, which unlink basic motor activities and reveal their interdependence. Natural variants can also be exploited to provide unexpect ed information about motor function. This general approach to uncovering pr otein function by analysis of informative mutants is applicable not only to molecular motors, but to other proteins of interest.