Biomolecular Motors

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Biomolecular motors

Directed motion versus diffusion

•Bionanomachinery, however, motors are remarkably rare

• Motion is accomplished by diffusion and capture, without the need for directed motion

• Motors are employed for micrometer and meter scale movement- separation
of chromosomes, remodeling of cell organelles, contraction of our muscles etc.

• Departure from the norm- Kinesins, ATP synthase


ATP Powers Linear Motors

• Linear motion along a fixed track


• Myosin, which moves along actin filaments, and kinesin, which moves along
Microtubules.
• Each myosin molecule performs one “power stroke” at a time: It binds to actin,
pulls on it, and then dissociates.
• Lot of myosin molecules need to work in concert
• Large array of myosin, each must perform its power stroke and then
get out of the way to allow the neighboring molecules to do their jobs
• Kinesin walks along the microtubule making many successive steps- Locomotive
that pulls cargo along the microtubule

Myosin
Myosin

• Motor domain is elongated with a site for binding ATP- Catalytic domain
• At rest its bend and can accept an ATP and holds the actin
• ATP is hydrolysed when the Pi vacates it straigtens- Power stroke and
dissociates fro actin
• The different cargo in catalytic site changes the relay loops which acts on the
converter domain- bringing about a larger change
• Change is amplified by lever arm a major shift of 100A 0
Motor domain

Rest Power stroke


Kinesin

• Different cargo (ATP/ADP) on the motor make a linker a Neck linker ordered or disordered
• Two sensor loops that constitute the relay helix – transduces information
• ATP cleaved, Pi hydrogen bond in the catalytic site- A switch- when the interaction is
is broken
Kinesin
ATP synthase

• Nature has also developed nanoscale rotary motors


• ATP synthase is a combination of two motors, termed F0 and F1
• Two different fuels- The F0 motor is powered by a proton electrochemical gradient
F1 motor is powered by ATP
• In the complex, the two motors are connected so that it acts as both a motor
and a generator.
• Motion of F0 driven by proton flow can be used to generate ATP in F1.
• ATP-powered motion of F1 can be used to turn F0 and pump protons, creating an
electrochemical gradient.
F0

• Motor is composed of a cylindrical rotor, with 10–14 identical


subunits and a stator that associates with one side of the rotor
• The entire complex must be embedded in a lipid bilayer membrane
• The rotor will naturally perform a rotational random walk, making
small random steps forward and backward under the power of thermal motions
• The trick is to favor steps in the forward direction and to block steps
in the reverse direction
• The proton-driven F0 motor contains an acidic aspartate amino acid on the
surface of the cylinder.
• Proton from one side of the membrane enters and neutralises the aspartate
• The rotor moves and and encounters the exit channel where it deposits the
proton.
• The process is entirely reversible- can pump protons on either directions
ATP synthase
F1

• F1 is composed of a ring of six subunits, three alpha subunits and three beta subunits
• An axle runs through the center of the ring, pressing differently on the three
beta subunits and changing their structure.
• The different conformations of the -subunit have markedly different affinity for ATP.
• Each rotation of 120° occurs in two steps
• When rotation is powered by ATP, a 90° rotation happens
• The ATP then hydrolyzes into ADP.. the dissociation of ADP then fuels a 30° rotation.
• The movement is reversible
• The forcible rotation of the axle first increases the affinity for ADP,
which combines with phosphate to form ATP without change in conformation,
and further rotation forces ATP to be released.
• In proton pump- The F1 rotes by ATP hydrolysis
• When acting as a motor, ATP is easy to bind to the motor but difficult to release
and ADP is difficult to bind but easy to release.
Flagellar motor

• Motor that spin flagella in both directions


• 100,000 rpm and driving cells at speeds exceeding hundreds of micrometers
per second.
• Proton gradient powers the motor or in certain case sodium
• Multiple motor and stator units are involved
• Approximately 400 force-generating steps provide one rotation
and require transfer of about 1200 protons across the membrane
Brownian ratchet and thermal motion

• The nanoscale world is dominated by thermal motions, and, not surprisingly,


cells have developed machines that capture thermal energy and use it to
do work.
• The trick is to create a machine that rectifies random thermal motion
• Passage to control a random walk anology
• In F0 the movement of protons in one direction is a ratchet
•The best-characterized example of a Brownian ratchet is actin, which is
used in the crawling of cells
Actin filaments, using ATP to drive the transition from free subunits to assembled
Polymer
• As the membrane moves space for actin to insert glued in place by ATP

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