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Molecular motors

Molecular motors. Biological molecular machines that are the essential agents of movement in living organisms. wiki. Motor proteins. Discovered some 25 years ago Original definition covers 3 classes Kinesins Myosins Dyneins. BACKGROUND: STRYER 6th ed CHAPTER 34

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Molecular motors

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  1. Molecular motors Biological molecular machines that are the essential agents of movement in living organisms wiki

  2. Motor proteins • Discovered some 25 years ago • Original definition covers 3 classes • Kinesins • Myosins • Dyneins BACKGROUND: STRYER 6th ed CHAPTER 34 Mol.Biol. Of THE CELL 4th ed. pp 949-969

  3. Mol. motor definition • A protein that transforms ATP energy into mechanical energy or motion • Motion occurs through reversible association-dissociation steps on protein array or surface of cellular sub-structure

  4. Types of motors • Rotation -------- ATP synthase / ATPase • Procession ----- Kinesin /microtubules • Tension -------- Myosin/ actin GENERAL PRINCIPLE: Conformational change translated into an organised effect

  5. FUNCTIONS • Cell movement • Transport of organelles • Protein transport through membranes • Pumps

  6. The Kinesin Family linear motors http://www.cellbio.duke.edu/kinesin • ATP-driven, • active transport • along microtubules • functions: • spindle formation • chromosome separation • vesicle transport

  7. Conventional Kinesin It’s a dimer stalk neck-linker motor domain tail You need twolegs to walk 50 nm

  8. Effect on larval locomotion wild-type Drosophila larva Drosophila larva with kinesin heavy chain (Khc) mutation

  9. Conventional Kinesin Model for all kinesins? • vesicle transport • 8 nm steps • moves in the +direction • can work against ~6 pN • makes >100 steps • processive: 10 µs per step • speed ~ 800 nm/s See for details: Shao & Gao (May 2006) PNAS 103 (21):8072-8077

  10. Moves to - end Moves to + end

  11. Catalytic domains KHC (kinesin-1, or conventional kinesin) Ncd (kinesin-14 family)

  12. Catalytic core: Ncd loops in blue, Kinesin red

  13. Neck linker fixed Neck linker free

  14. Structural Basis Of Motility KINESIN hand over hand inchworm Source Erwin Peterman UVA

  15. Floppy logic (non-equivalent steps) Twisting model (equiv.steps) Alternate sites model (nonequiv. Steps)

  16. Movie kinesin

  17. Visualization of movement Alternative: fix support (protein) and observe microtubule

  18. Fast movements back and forth Slow process with cargo Motion is strongly force-dependent

  19. Muscle Action: Myosin

  20. Myosin II model • skeletal muscle contraction • 5 nm power stroke • in the +direction of actin • works with hundreds together • non processive

  21. Myosin II fast skeletal muscle

  22. ADP ATP ATP ADP, Pi microtuble actin ADP,Pi ADP ATP Myosin II vs Kinesin Power stroke Power stroke ADP Pi Pi ADP ATP hydrolysis not driving power stroke ATP hydrolysis driving power stroke Energy stored in free protein and released after actin binding Energy released in bound protein resetting to original state in solution

  23. ADP ATP ADP, Pi ATP microtuble actin ADP,Pi ADP ATP Myosin vs Kinesin Power stroke Power stroke ADP Pi Pi ADP Concerted action Independent action

  24. Discussion of paper Research goal? Only one goal in paper or fuzzy? How important is goal in the field? Approach Proper techniques/alternatives? Conclusions In line with data? Additional exp’s needed? Future New opportunities arising from the paper? Which?

  25. Some more movies… Hunt Nature invented wheels

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