A NEW YOUTH FOR MYOSINS

The first two crystalline structures of the myosin head were recently published. The myosin head is made of two main domains. The motor doma in comprises the first 600 N-terminal residues of the myosin head heav y chain; it contains the ATP-binding site and the main interface with actin. The transmission domain is composed of the long helicoidal C-te rminal part of the myosin head heavy chain, along with essential and r egulatory light chains. New motility assays demonstrated the movement and force produced by a single myosin molecule along the actin filamen t. Genetics and protein engineering led to the production of chimeric myosin molecules. These combined techniques enabled to demonstrate tha t the motor domain of the myosin head in skeletal muscles is self-suff icient for hydrolyzing ATP and inducing movement, and that the presenc e of light chains is crucial for motility efficiency by stabilizing th e transmission domain. In contrast, light chains in non-striated muscl e or non-muscle myosins determine motor activity by regulating ATP hyd rolysis but do not markedly influence motile performances of the corre sponding muscles. Such studies on the myosin structure and structure-f unction relationships between heavy and light myosin subunits helped t o redefine the specific role of certain myosin domains. All these adva nces have generated renewed interest in the field of biological motor molecules and myosin isoforms. The discovery of point mutations in the ventricular myosin heavy chains from patients with familial hypertrop hic cardiomyopathy has accelerated new research projects in this promi sing field!