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

2/1/2012 At the heart of a Motor … 3D Protein Conformation Molecular Motors Roop Mallik What is a Molecular Motor ? Why should you care about Molecular Motors • Generates Mechanical Motion using Biologists – Electrical energy – Essential proteins – Chemical energy – Important for myriad biological processes • “Mechanochemical” Enzyme y Physicists/Engineers Physicists/Engineers • Motion drives metabolic functions – Robust and efficient nanoscale machines • Essential, Robust, Varied Can we make our own ? • Works at Molecular Level … Nano Health • Artificial “Motors” have been made – Motor Neuron degeneration, Body asymmetry… What kind of motion do Motors generate ? Rotary Molecular Motors Linear or Use of Genetic Information DNA (RNA Polymerase) based Making Proteins (Ribosome) Moving muscles (Myosin) Protein based Moving things in the cell http://www.sciencedaily.com (Myosin, Kinesin, Dynein) Rotary Protein 1

2/1/2012 Rotary Motors play a critical role in your body … Making ATP … The Rotary F O F 1 ATP synthase motor • They make the linear motors work • ATP is the energy source … Respiration Glucose ATP A-p-p-p + H 2 O A-p-p + P i + H + ENERGY ATP 10 -19 Joules = 25 kT = 100 pN-nm ADP+Pi H + Mitochondrion Unitary Biological forces are ~ picoNewtons http://www.sciencenews.org/ Experimental approaches to understand F 1 -- ATPase Linear Motors as ATPases Rower Porter ATP ATP ATP ATP DUTY RATIO Rower ~ 0.01 Movie Porter ~1 Watanabe et al, 2008 Rowers – Muscle Myosin Spudich, 2001 Large Linear arrays � Rapid Motion Movie from Ron Vale group http://www.humanisamiracle.com/ 2

2/1/2012 Porters: The need for long range Transport Diffusion does not help… Time for diffusion ~ x 2 / 2 D ; D = k b T / 6 πη R D = Diffusion constant; x = Distance moved; k b = Boltzmann constant; T = Temp; η = Viscosity; R = Dimension D ~ 1 micron 2 /sec for 50 nm diameter 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 … Changing colour Rodionov et al, Current Biology (2003) Dispersed Aggregated M. A. Welte, 2004 What is it like to be a Motor inside the Cell ? Motors walk on stepping stones They know which way to go … Cargo + − α β Overdamped motion 3

2/1/2012 Magnitudes… 50 nanometers http://www.imb-jena.de/~kboehm • Typical displacements ~ 10 nm CARGO – Human hair ~ 100,000 nm • Typical forces ~ PicoNewtons (10 -12 N) • Velocity ~ 1 micron/sec (100 mm/day) Hirokawa et al, 2005 • Kinesin - step occurs every 8 msec on an average Models … Ait-Haddou and Herzog,2003 Thermal Ratchet Powerstroke Force = – K • x Optical Trap 10 seconds Crevel et al, 1999 4

2/1/2012 Rowers -- Force, Working stroke measurements MYOSIN - II Finer et al, 1994 Probabilistic ATP binding Porters and their force generation Myosin V Goat Kinesin moving on Goat Microtubules 5 microns 1 2 3 3 4 4 F motor F Trap Veigel et al Objective Hand over Hand or Inchworm ? et al et al 5

2/1/2012 Myosin and Kinesin … Same at the Core MYOSIN V KINESIN MYOSIN V KINESIN Vale and Milligan, 2000 6