Molecular Motors Roop Mallik What is a Molecular Motor ? Why - - PDF document

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Molecular Motors

Roop Mallik

At the heart of a Motor … 3D Protein Conformation

• Generates Mechanical Motion using

– Electrical energy – Chemical energy

• “Mechanochemical” Enzyme

What is a Molecular Motor ? y

• Motion drives metabolic functions
• Essential, Robust, Varied
• Works at Molecular Level … Nano
• Artificial “Motors” have been made

Biologists

– Essential proteins – Important for myriad biological processes

Physicists/Engineers

Why should you care about Molecular Motors

Physicists/Engineers

– Robust and efficient nanoscale machines

Can we make our own ?

Health

– Motor Neuron degeneration, Body asymmetry… What kind of motion do Motors generate ?

Linear

• r

Use of Genetic Information (RNA Polymerase) Making Proteins (Ribosome) DNA based Moving muscles (Myosin) Moving things in the cell (Myosin, Kinesin, Dynein) Protein Protein based

Rotary Rotary Molecular Motors

http://www.sciencedaily.com

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Rotary Motors play a critical role in your body …

• They make the linear motors work
• ATP is the energy source …

Glucose ATP

Respiration A-p-p-p + H2O A-p-p + Pi + H+

10-19 Joules = 25 kT = 100 pN-nm

ENERGY

Unitary Biological forces are ~ picoNewtons

Making ATP … The Rotary FOF1 ATP synthase motor

http://www.sciencenews.org/

Mitochondrion

H+ ADP+Pi ATP

Experimental approaches to understand F1 -- ATPase

ATP ATP ATP ATP

Movie

Watanabe et al, 2008

Linear Motors as ATPases

Rower Porter

DUTY RATIO Rower ~ 0.01 Porter ~1 Rowers – Muscle Myosin

Large Linear arrays Rapid Motion

http://www.humanisamiracle.com/

Spudich, 2001

Movie from Ron Vale group

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Porters: The need for long range Transport

Time for diffusion ~ x2 / 2D ; D = kbT / 6πηR

D = Diffusion constant; x = Distance moved; kb = Boltzmann constant; T = Temp; η = Viscosity; R = Dimension

D ~ 1 micron2/sec for 50 nm diameter

Diffusion does not help…

D 1 micron /sec for 50 nm diameter synaptic vesicle in Neuron To travel 1 metre : Need ~ 16,000 years

Need active linear transport An example of Transport …

• M. A. Welte, 2004

Rodionov et al, Current Biology (2003)

Changing colour

Dispersed Aggregated

What is it like to be a Motor inside the Cell ? Overdamped motion

Motors walk on stepping stones

α β

− +

Cargo

They know which way to go …

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50 nanometers

http://www.imb-jena.de/~kboehm Hirokawa et al, 2005

Magnitudes…

• Typical displacements ~ 10 nm

– Human hair ~ 100,000 nm

• Typical forces ~ PicoNewtons (10-12 N)

CARGO

• Velocity ~ 1 micron/sec (100 mm/day)
• Kinesin - step occurs every 8 msec on an average

Models …

Ait-Haddou and Herzog,2003

Thermal Ratchet Powerstroke

Optical Trap

Force = – K • x

Crevel et al, 1999

10 seconds

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Rowers -- Force, Working stroke measurements

Finer et al, 1994

MYOSIN - II

Probabilistic ATP binding

Porters and their force generation

Goat Kinesin moving on Goat Microtubules

5 microns 1 2 3 4

Fmotor FTrap

Objective 3 4

Myosin V

Veigel et al

Hand over Hand or Inchworm ?

et al et al

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MYOSIN V KINESIN MYOSIN V KINESIN

Myosin and Kinesin … Same at the Core

Vale and Milligan, 2000