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

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
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 two legs 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):

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

25. Myosin II vs Kinesin ADP ATP ADP,Pi Power stroke Power stroke ADP Pi
actin
microtuble
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

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

28. 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?

29. Some more movies…
Hunt
Nature invented wheels