Molecular Motors Lecture 33`BSCI 420/421Nov 18, 2002 “To survive the 21 st century, our thinking must be creative and humane as well as analytical.” - Robert Kuhn 1.Myosins 2.Kinesins 3.Dyneins

1.Myosins Are a family of motor proteins that bind to & move along actin filaments toward the + ends. Large globular heads bind and split ATP Undergo a configurational change that changes the angle of the head with respect to an  -helical tail. E.g. Myosin II

Myosin II of vertebrate muscle

The Myosin family portrait N C

In vitro motility assay: Evidence of myosin’s motor activity (Fig. 53) (wrong way)

X-ray crystal structures of myosin & kinesin heads

Myosin cross-bridge cycle

Skeletal Muscle fibers are multinucleate muscle cells formed by fusion of myoblasts. (fig 68)

Sarcomere structure of myofibrils, dark=A band, light=I band

X-sec of myofibril, insect flight muscle, verts slightly different. (Fig.70)

 -actinin Sliding filament model (Fig.71)

MT-based Motors: Kinesin & Dynein Kinesin is a large protein with 4 polypeptide chains Like myosin it has 2 heavy chains, each w a globular head domain and long  -helical tail. 2 light chains on cargo- MTbinding end binding(vary in diff. cells w diff. cargo) ATP-binding siteCoiled-coil in each head tail

Kinesins + KIFs - (Kinesin Family + members + Freeze- Etched, Shadowed TEM + 2 HC in tail

Comparison of kinesin and myosin mechanochemical cycles

3. Dyneins are a family of minus end directed MT motors. Largest and fastest molecular motors (14  m/sec vs 2  m/sec for kinesin)(fig 56)

Dynein moves vesicles and the Golgi app toward the cell center. A)Untreated B) Nocodazole Fig. 62