Myosin based motuity-structural studios of the dictyostelium discoideum myosin motor domain

The manner in which chemical energy is coaverted into directed movement in muscle has long been viewed as one." of the most intriguing fundamental questions in biochemistry. A great deal of progress has been made over the past several decades toward understanding this process including, more recently, the determination of the three dimensional structtlres of both actin and myosin subfragment-1. In addition, the crystal structures of a genetically truncated myosin head complexed with substrate anaiogs such as MgPPi, MgADPBeFx, MgADPVO4, and MgADPAIF4 have given good insight into how ATP hydrolysis is related to movement. Despite this progress, however, a number of questions still remain unanswered. With this in mind we are continuing to investigate the solid state structures of a truncated myosin head complexed: 1) with a variety of new substrate analogs such as MgADP, MgATPgamaS, and MgAMPPNP; 2) with non-nucleotide substrates which support tension; and 3) in the absence of substrate. In addition, we are investigating the structures of several biologically important myosin mutant complexes which a) were specifically designed to test the current hypotheses on how ATP hydrolysis is related to movement or b) have specific importance because of their known presence in motor protein related disorders such as Usher syndrome.