Molecular motors

Molecular motorsMolecular motors

Biological molecular machines that are the essential agents of movement in living organismswiki

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:GENERAL PRINCIPLE:

Conformational change translated Conformational change translated into an organised effectinto an organised effect

FUNCTIONS

• Cell movement• Transport of organelles• Protein transport through membranes• Pumps

The Kinesin Family linear motorsThe Kinesin Family linear motors

ATP-driven,

active transport

along microtubules

functions:

• spindle formation

• chromosome separation

• vesicle transport

http://www.cellbio.duke.edu/kinesin

Conventional KinesinConventional Kinesin

tail

stalk

neck-linker

motor domain

It’s a dimer

You need two legs to walk

50 nm

Effect on larval locomotion

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wild-type Drosophila larva Drosophila larva with kinesin heavy chain (Khc) mutation

Conventional Kinesin Conventional Kinesin Model for all kinesins?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

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

Catalytic domains

Ncd loops in blue, Kinesin red

Catalytic core:

Neck linker fixed Neck linker free

Structural Basis Of MotilityStructural Basis Of MotilityKINESIN

hand over hand inchworm

Source Erwin Peterman UVA

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Floppy logic (non-equivalent steps) Twisting model (equiv.steps)

Alternate sites model (nonequiv. Steps)

Movie kinesin QuickTime™ and a

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Visualization of movementVisualization of movement

Alternative: fix support (protein) and observe microtubuleAlternative: fix support (protein) and observe microtubule

Slow process with cargo

Motion is strongly force-dependent

Fast movements back and forth

Muscle Action: Muscle Action: MyosinMyosin

Myosin II model

• skeletal muscle contraction

• 5 nm power stroke

• in the +direction of actin

• works with hundreds together

• non processive

Myosin IIMyosin IIfast skeletal muscle

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Myosin II vs KinesinADP,Pi ADP

microtubleactin

ADPATP

Power stroke

ATP

ATP hydrolysis not driving power stroke ATP hydrolysis driving power stroke

Power stroke

ATP

ADPPiADP

ADP, Pi

Pi

Energy stored in free proteinand released after actin binding

Energy released in bound proteinresetting to original state in solution

Myosin vs KinesinADP,Pi ADP

microtubleactin

ADPATP

Power stroke

ATP

Power stroke

ATP

ADPPiADP

ADP, Pi

Pi

Concerted action Independent action

Discussion of paperDiscussion of paper

Research goal?Only one goal in paper or fuzzy?How important is goal in the field?

ApproachProper techniques/alternatives?

ConclusionsIn line with data?Additional exp’s needed?

FutureNew opportunities arising from the paper?Which?

Some more movies…

Hunt

Nature invented wheels

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