Myosin V complexed with calmodulins
Gallus gallus (chicken)
Myosin is a motor protein that plays key roles in various functions such as muscle contraction (myosin II, MyoII) or vesicle transport (myosin V, MyoV). MyoV moves along actin filaments to transport organelles, vesicles and mRNAs using the energy of ATP hydrolysis. In its activated state, MyoV works in a hand-over-hand manner and delivers its cargo to the barbed (+) end of the actin filament.
The mechanism by which the MyoV returns to the start position after cargo delivery remains unknown. However, the inactive structure described here indicates a recycling mechanism for MyoV by "running up the down escalator". The "down escalator" is the actin filament, which moves in the opposite direction from activated MyoV by the treadmilling process. The activated MyoV with cargo moves quickly along the actin filament by using the energy of ATP. When it reaches the actin (+) end, it puts off the cargo and goes back to the start position through the "escalator" (Fig. 1).
The inactivated MyoV has a compact structure compared to its activated state. This structure has been determined by using cryoelectron tomography images on which known PDB structures are superimposed.
MyoV has two chains that have motor domains on the amino-terminal heads, followed by lever arms with 6 calmodulin molecules. After that, it has a coiled-coil dimerization domain (S2) and a carboxy-terminal cargo-binding domain (Fig. 2). It should be noticed that although the cargo binding domain-like structures were observed on cryoelectron tomography images, these domains were omitted due to the lack of the structure in the PDB.
The inactivated MyoV folds at the border of its lever arm and coiled coil regions, and a binding occurs between the motor and cargo domains. The actin binding region of the motor domain is still free because the cargo domain binds to the loop 1 region of the motor domain. Thus, the motor domain can bind to actin filaments even in the inactivated state and, in fact, this structure was also observed.
It is expected in the future that an X-ray structure of inactivated MyoV be solved and that the various kinds of its binding pattern to actin be identified. It is hoped that eventually a series of MyoV dynamics is elucidated.
Protein Data Bank (PDB)
Liu, J. Taylor, D.W. Krementsova, E.B. Trybus, K.M. Taylor, K.A.; "Three-dimensional structure of the myosin V inhibited state by cryoelectron tomography"; Nature; (2006) 442:208-211 PubMed:16625208.
author: Naoya Fujita