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Kinesin Sara Van Nortwick Geometric Computations in Molecular Biology SS 2007 ETH

Kinesin Sara Van Nortwick Geometric Computations in Molecular Biology SS 2007 ETH. The Structure. X-ray crystallography by Kull et al. (1996) Resolution = 1.8 A Dimer. Let’s Motor!. The Family of Motor Proteins Large and varied responsibilities Unidirectional movement Fuel = ATP

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Kinesin Sara Van Nortwick Geometric Computations in Molecular Biology SS 2007 ETH

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  1. KinesinSara Van NortwickGeometric Computations in Molecular BiologySS 2007ETH

  2. The Structure • X-ray crystallography by Kull et al. (1996) • Resolution = 1.8 A • Dimer

  3. Let’s Motor! • The Family of Motor Proteins • Large and varied responsibilities • Unidirectional movement • Fuel = ATP • Share motor “head” domain (structural core, common ancestor)

  4. Where are we Going and Why? • Center Periphery • Compass = Microtubule Polarity • Anterograde Transport (towards the positive) • Point A to Point B • Kinesin > Diffusion • Alignment • Mitosis (cell division)

  5. How Fast are we Talking? • 2 um/sec • 8 nm per step (spacing of tubulin dimers along the microtubule) • = 250 steps/second! • Protein head = 7.5 X 4.5 X 4.5 nm • ≈ speed and thrust of the supersonic car • 60% efficiency

  6. The Motor in Action • Kinesin Movement Video: • http://www.scripps.edu/cb/milligan/research/movies/kinesin_mov.html

  7. Many Varieties… • Motor domain conserved @ N-terminus • 40 known variations in Humans • Differences in adaptor structure between motor and the object to be moved

  8. Two heavy chains comprise globular head Light Chains comprise cargo binding region Breaking it Down

  9. Motor domain is similar in both motor proteins Very little amino acid similarity Kinesin is 340 aa while myosin is 850 aa RMS of 3.5 A for 183 aa of kinesin motor domain Kinesin Vs. Myosin

  10. Structure Isn’t Always Enoguh…

  11. References • Kozeilski, Sack, et al. The Crystal Structure of Dimeric Kinesin and Implication fo Microtubule-Dependent Motility. Cell, Vol 91, 985-994. December, 26, 1997. • Molecular Biology of the Cell http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.3054 • PDB Molecule of the Month • Kull, Sablin, et al.(1996). Crystal structure of the kinesin motor domains reveals a structural similarity to myosin. Nature 380, 550-554. • Wikipedia • Block, Steve. Kinesin: What Gives? Cell, Vol 93 5-8. April, 1998.

  12. We’ve Arrived… Questions?

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