Kinesins and dyneins
• Cytoskelton includes two components in addition to
actin: intermediate filaments and microtubules.
• Microtubules act as tracks for two classes of motor
proteins: kinesins and dyneins.
– Kinesins: moving along microtubules usually carry cargo
such as organelles and vesicles from the center of a cell to
– Dyneins: important in sliding microtubules relative to one
other during the beating of cilia and flagella on the
surfaces of some eukaryotic cells. They carry cargo from
periphery to centre of cell.
Microtubules are a component of the cytoskeleton.
These cylindrical polymers of tubulin can grow as long
as 25 micrometers and are highly dynamic.
The outer diameter of microtubule is about 25 nm.
• Microtubules are long, hollow cylinders made up of polymerised α- and β-tubulin
• They are highly dynamic structures that grow through the addition of α- and β-
tubulin dimers to the ends of existing structures.
• Like actin, tubulins also bind and hydrolyze nucleoside triphosphates, although for
tubulin the nucleotide is GTP rather than ATP.
• Thus, a newly formed microtubule consists primarily of GTP-tubulins.
• Through time, the GTP is hydrolyzed to GDP.
• The GDP-tubulin subunits in the interior length of a microtubule remain stably
polymerized, whereas GDP subunits exposed at an end have a strong tendency to
• Thirteen protofilaments associate laterally to form a single microtubule and this
structure can then extend by addition of more protofilament
The heavy chain of kinesin-1 comprises a globular head (the motor domain) at
the amino terminal end connected via a short, flexible neck linker to the stalk – a
long, central alpha-helical domain – that ends in a carboxy terminal tail domain
which associates with the light-chains
The head regions bind to microtubules and also bind ATP. The head domains
are thus ATPase motors.
The tail domain binds to the organelle to be moved. ATP is needed for both
binding and movement. Hydrolysis is absolutely essential for movement.
Kinesin Motion is highly processive
• Kinesins are motor proteins that move along microtubules.
• When a kinesin molecule moves along a microtubule, the
two head groups of the kinesin molecule operate in
tandem: one binds, and then the next one does.
• A kinesin molecule may take many steps before both heads
groups are dissociated at the same time.
• A single kinesin molecule will typically take 100 or more
steps toward the plus end of a microtubule in a period of
seconds before the molecule becomes detached from the
• The average step size is approximately 80 Å, a value that
corresponds to the distance between consecutive α- or β-
tubulin subunits along each protofilament.
Kinesin movement along microtubule
• The addition of ATP strongly increases the
affinity of kinesin for microtubules.
• This is in contrast with the behavior of myosin;
ATP binding to myosin promotes its
dissociation from actin.
• In a two-headed kinesin molecule in its ADP form,
dissociated from a microtubule, the neck linker binds the
head domain when ATP is bound and is released when ADP is
• The initial interaction of one of the head domains with a
tubulin dimer on a microtubule stimulates the release of ADP
from this head domain and the subsequent binding of ATP.
• The binding of ATP triggers a conformational change in the
head domain that leads to two important events.
• First, the affinity of the head domain for the microtubule
increases, essentially locking this head domain in place.
• Second, the neck linker binds to the head domain.
• This change repositions the other head domain acting
through the domain that connects the two kinesin
• In its new position, the second head domain is close to a
second tubulin dimer, 80 Å along the microtubule in the
direction of the plus end.
• Meanwhile, the intrinsic ATPase activity of the first head domain
hydrolyzes the ATP to ADP and Pi.
• When the second head domain binds to the microtubule, the first
head releases ADP and binds ATP.
• Again, ATP binding favors a conformational change that pulls the
first domain forward.
• This process can continue for many cycles until, by chance, both
head domains are in the ADP form simultaneously and kinesin
dissociates from the microtubule.
• Because of the relative rates of the component reactions, a
simultaneous dissociation occurs approximately every 100 cycles.
• Kinesin hydrolyzes ATP at a rate of approximately 80 molecules per
• Thus, given the step size of 80 Å per molecule of ATP, kinesin moves
along a microtubule at a speed of 6400 Å per second. This rate is
considerably slower than the maximum rate for myosin, which
moves relative to actin at 80,000 Å per second
Kinesin ‘walks’ along the microtubule
while carrying its cargo
• First microtubule motors to be identified.
• Very large in size.
• Dyneins are called "minus-end directed
motors, because directed towards minus end
Dynein is a motor protein in cells which converts the chemical
energy contained in ATP into the mechanical energy of
Dynein transports various cellular cargo by "walking" along
cytoskeletal microtubules towards the minus-end of the
They transport cargo from the periphery of the cell towards the
Two types: cytoplasmic dyneins and axonemal dyneins.
• Cytoplasmic dynein probably helps to position
the Golgi complex and other organelles in the
• It also helps transport cargo needed for cell
function such as vesicles made by the
endoplasmic reticulum, endosomes, and
• Dynein is involved in the movement of
chromosomes and positioning the mitotic
spindles for cell division.
• Present in flagella or cilia of eukaryotes.
• Help in their beating for effective movement.
• Flagella are usually 1 or 2 per cell.
Generally longer. Have rotary motion.
• Cilia are usually many per cell.
They tend to have a whip-like movement.
Cilia & flagella
Bounded by plasma
Basal body: a single centriole
cylinder at the base of each
cilium or flagellum.
Core axoneme: a complex of
microtubules & associated
• Each dynein molecule forms a cross-bridge
between two adjacent microtubules of the ciliary
• During the "power stroke", which causes
movement, the ATPase motor domain undergoes
a conformational change that causes the
microtubule-binding stalk to turn relative to the
cargo-binding tail with the result that one
microtubule slides relative to the other .
• This sliding produces the bending movement
needed for cilia to beat and propel the cell or
• Groups of dynein molecules responsible for
movement in opposite directions are probably
activated and inactivated in a coordinated fashion
so that the cilia or flagella can move back and
–Is responsible for the bending movement
of cilia and flagella
Powered by ATP, the dynein arms of one microtubule doublet
grip the adjacent doublet, push it up, release, and then grip again.
If the two microtubule doublets were not attached, they would slide
relative to each other.
In a cilium or flagellum, two adjacent doublets cannot slide far because
they are physically restrained by proteins, so they bend. (Only two of
the nine outer doublets in Figure 6.24b are shown here.)
Figure 6.25 B
Localized, synchronized activation of many dynein arms probably causes a bend to begin
at the base of the Cilium or flagellum and move outward toward the tip. Many successive
bends, such as the ones shown here to the left and right, result in a wavelike motion. In
this diagram, the two central microtubules and the cross-linking proteins are not shown.
Figure 6.25 C
• Several reports suggest bidirectional movement of
specific dyneins but no conclusive evidence of
unidirectional plus-end motility.
• Motility can be switched to unidirectional minus end
transport by phosphorylation.
• Probability that phosphorylation of motor regulates
• Positive End Directed motors: move from –ve
to + end.
Eg: Myosin and Kinesin Motors
• Negative End Directed motors: move from
+ve end to –ve end