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 Mol.Biol. Of THE CELL 4th ed. pp 949-969

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

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

FUNCTIONS Cell movement Transport of organelles Protein transport through membranes Pumps

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

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

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

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

Moves to - end Moves to + end

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

Catalytic core: Ncd loops in blue, Kinesin red

Neck linker fixed Neck linker free

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

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

Movie kinesin

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

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

Muscle Action: Myosin

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

Myosin II fast skeletal muscle

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

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

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?

Some more movies… Hunt Nature invented wheels