Molecular Motors

objectives
• Describe molecular motors’ class, structure and
functions.
 Molecular motors
• Molecular motors are composed of motor proteins.
• These proteins bind to a polarized cytoskeletal filament
and use the energy derived from repeated cycles of
ATP hydrolysis to move steadily along it.
• Power movements of subcellular components
• Create local forces leading to cell shape changes
(Muscle contraction)
• Power cell movements
• Dozens of different motor proteins coexist in
every eukaryotic cell
• They differ in the type of filament they bind
to (either actin or microtubules), the
direction in which they move along the
filament, and the cargo they carry.
 Classification

• There are 3 classes of molecular motors

1. kinesin,
2. dynein, and
3. myosin.
 Kinesin
• kinesin is a double headed molecule that tends to
move its “cargo” toward the + ends of microtubules.
• Dimer of two heavy chains; each heavy chain
complexes with a light chain
• Three domains
• Two globular head domains
• Long central coiled-coil stalk
• Two small globular tail domains (contain light chains)
• Kinesin accomplishes transport by "walking" along a
microtubule
• In the "hand-over-hand" mechanism, the kinesin heads
step past one another, alternating the lead position.
• One head binds to the microtubule and then bends its
neck while the other head swings forward and binds,
producing almost continuous movement
• In the "inchworm" mechanism, one kinesin head
always leads, moving forward a step before the trailing
head catches up.
 Dynein
• Dynein transports various cellular cargo by
"walking“ along cytoskeletal microtubules
towards the minus-end of the microtubule.
• Composed of two or three heavy chains (that
include the motor domain) and a large and
variable number of associated light chains.
• cytoplasmic dyneins and axonemal dyneins,
which are also called ciliary or flagellar dynein
• Cytoplasmic dynein are found in all eukaryotic
cells - important for vesicle trafficking, and for
localization of the Golgi apparatus near the
center of the cell.
• Axonemal dyneins, are highly specialized for the
rapid and efficient sliding movements of
microtubules that drive the beating of cilia and
flagella.
• Dyneins are the largest of the known molecular
motors, and they are also among the fastest.
 Myosin
• Myosins comprise a family of ATP-dependent motor proteins and are
best known for their role in muscle contraction and their involvement
in a wide range of other eukaryotic motility processes.
• Most myosin molecules are composed of a head, neck, and tail
domain.
• The head domain binds the filamentous actin, and uses ATP hydrolysis
to generate force and to "walk" along the filament towards the barbed
(+) end (with the exception of myosin VI, which moves towards the
pointed (-) end).
• The neck domain acts as a lever arm for transducing force generated by
the catalytic motor domain.
• The tail domain generally mediates interaction with cargo molecules
and/or other myosin subunits. In some cases, the tail domain may play
• 18 different families (identified by genetic analysis) with
different functions:
• Myosin II powers muscle contraction and cytokinesis
• Myosins I transport of endocytic vesicles
• Myosin V phagocytosis and transport of cellular
elements
• Myosins VI and VII – transport endocytic vesicles into
the cell. Found in the inner ear and mutations in the
gene coding for myosin VII cause deafness in mice and
humans.
 Myosin II
• A myosin II molecule is composed of two heavy
chains (each about 2000 amino acids long and
four light chains.
• the long coiled-coil tail bundles itself with the tails
of other myosin molecules forming bipolar ―thick
filaments that have several hundred myosin
heads, oriented in opposite directions at the two
ends.
• Cyclic attachment and detachment of myosin head
from actin filament is each coupled to one ATP
hydrolysis.
• ATP binding to myosin opens the cleft and disrupts
actin binding and releases an actin from myosin
head
• ATP hydrolysis - bending of the head to the new
position (generation of movement)
• After ATP hydrolysis the cleft closes on the next
actin molecule.