Molecular MotorsLecture 33 ` BSCI 420/421 Nov 18, 2002

“To survive the 21st century, our thinking must be creative and humane as well as analytical.”

- Robert Kuhn

1. Myosins2. Kinesins3. 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 portraitN--------------------------------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 chainson cargo-

MT binding endbinding (vary in diff.

cells w diff.cargo)

ATP-binding site Coiled-coilin each head tail

Kinesins +

KIFs -(KinesinFamily +members

+

Freeze-Etched,ShadowedTEM

+ 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 vs2 m/sec for kinesin)(fig 56)

Dynein moves vesicles and the Golgi app toward the cell center.

A) Untreated B) NocodazoleFig. 62